Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001083962.2(TCF4):c.1487-5G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8970178

235851 (ClinVar)

Gene: TCF4

Condition: Pitt-Hopkins syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e8140e43-27bd-4cc1-9309-aec2e4c5a0bb

Approved on: 2024-06-25

Published on: 2025-03-07

HGVS expressions

NM_001083962.2:c.1487-5G>A

NM_001083962.2(TCF4):c.1487-5G>A

NC_000018.10:g.55232676C>T

CM000680.2:g.55232676C>T

NC_000018.9:g.52899907C>T

CM000680.1:g.52899907C>T

NC_000018.8:g.51050905C>T

NG_011716.1:g.360954G>A

NG_011716.2:g.408318G>A

ENST00000354452.8:c.1487-5G>A

ENST00000635822.2:c.1529+1741G>A

ENST00000635990.2:n.1167-5G>A

ENST00000636400.2:c.1415-5G>A

ENST00000636751.2:c.*1195-5G>A

ENST00000636822.2:c.1097-5G>A

ENST00000637115.2:c.*1377-5G>A

ENST00000637169.2:c.839-5G>A

ENST00000637239.2:n.1554-5G>A

ENST00000637250.2:n.1181-5G>A

ENST00000637923.2:c.1085-5G>A

ENST00000638154.3:c.1514-5G>A

ENST00000643689.1:c.1097-5G>A

ENST00000674764.1:c.*1098-5G>A

ENST00000675707.1:c.1097-5G>A

ENST00000354452.7:c.1487-5G>A

ENST00000356073.8:c.1487-5G>A

ENST00000398339.5:c.1793-5G>A

ENST00000457482.7:c.1007-5G>A

ENST00000537578.5:c.1415-5G>A

ENST00000537856.7:c.1097-5G>A

ENST00000540999.5:c.1415-5G>A

ENST00000543082.5:c.1361-5G>A

ENST00000544241.6:c.1274-5G>A

ENST00000561831.7:c.1007-5G>A

ENST00000561992.5:c.1097-5G>A

ENST00000562680.5:n.1578-5G>A

ENST00000564228.5:c.1274-5G>A

ENST00000564403.6:c.1505-5G>A

ENST00000564999.5:c.1487-5G>A

ENST00000565018.6:c.1235-5G>A

ENST00000566279.5:c.1307-5G>A

ENST00000566286.5:c.1478-5G>A

ENST00000567880.5:c.1307-5G>A

ENST00000568673.5:c.1415-5G>A

ENST00000568740.5:c.1412-5G>A

ENST00000570177.6:c.1097-5G>A

ENST00000570287.6:c.1007-5G>A

ENST00000616053.4:c.1235-5G>A

ENST00000626466.1:n.522-5G>A

ENST00000626584.2:c.839-5G>A

ENST00000629387.2:c.1487-5G>A

NM_001083962.1:c.1487-5G>A

NM_001243226.2:c.1793-5G>A

NM_001243227.1:c.1415-5G>A

NM_001243228.1:c.1505-5G>A

NM_001243230.1:c.1478-5G>A

NM_001243231.1:c.1361-5G>A

NM_001243232.1:c.1274-5G>A

NM_001243233.1:c.1097-5G>A

NM_001243234.1:c.1007-5G>A

NM_001243235.1:c.1007-5G>A

NM_001243236.1:c.1007-5G>A

NM_001306207.1:c.1415-5G>A

NM_001306208.1:c.1274-5G>A

NM_003199.2:c.1487-5G>A

NM_001330604.2:c.1484-5G>A

NM_001330605.2:c.1097-5G>A

NM_001348211.1:c.1361-5G>A

NM_001348212.1:c.1097-5G>A

NM_001348213.1:c.1097-5G>A

NM_001348214.1:c.1004-5G>A

NM_001348215.1:c.839-5G>A

NM_001348216.1:c.1007-5G>A

NM_001348217.1:c.1415-5G>A

NM_001348218.1:c.1415-5G>A

NM_001348219.1:c.1415-5G>A

NM_001348220.1:c.1412-5G>A

NM_001243226.3:c.1793-5G>A

NM_001243227.2:c.1415-5G>A

NM_001243228.2:c.1505-5G>A

NM_001243231.2:c.1361-5G>A

NM_001243233.2:c.1097-5G>A

NM_001243234.2:c.1007-5G>A

NM_001243235.2:c.1007-5G>A

NM_001243236.2:c.1007-5G>A

NM_001330604.3:c.1484-5G>A

NM_001330605.3:c.1097-5G>A

NM_001348211.2:c.1361-5G>A

NM_001348212.2:c.1097-5G>A

NM_001348213.2:c.1097-5G>A

NM_001348214.2:c.1004-5G>A

NM_001348215.2:c.839-5G>A

NM_001348216.2:c.1007-5G>A

NM_001348218.2:c.1415-5G>A

NM_001348219.2:c.1415-5G>A

NM_001369567.1:c.1487-5G>A

NM_001369568.1:c.1487-5G>A

NM_001369569.1:c.1484-5G>A

NM_001369570.1:c.1484-5G>A

NM_001369571.1:c.1487-5G>A

NM_001369572.1:c.1487-5G>A

NM_001369573.1:c.1484-5G>A

NM_001369574.1:c.1484-5G>A

NM_001369575.1:c.1415-5G>A

NM_001369576.1:c.1412-5G>A

NM_001369577.1:c.1412-5G>A

NM_001369578.1:c.1412-5G>A

NM_001369579.1:c.1412-5G>A

NM_001369580.1:c.1412-5G>A

NM_001369581.1:c.1412-5G>A

NM_001369582.1:c.1415-5G>A

NM_001369583.1:c.1415-5G>A

NM_001369584.1:c.1412-5G>A

NM_001369585.1:c.1412-5G>A

NM_001369586.1:c.1418-5G>A

NM_003199.3:c.1487-5G>A

NM_001243230.2:c.1478-5G>A

Benign

PP3 BA1 BS2

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TCF4 Version 4.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The highest population minor allele frequency of the c.1487-5G>A variant in TCF4 in gnomAD v4.1 is 0.0016 in the Ashkenazi Jewish population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0003) for BA1, and therefore meets this criterion (BA1). The c.1487-5G>A variant is observed in at least 2 unaffected individuals (Internal database - Ambry) (BS2). The computational splicing predictor SpliceAI gives a score of 1 for acceptor loss, predicting that the variant disrupts the acceptor splice site of intron 16 of TCF4 (PP3). However, the resulting protein impact is minimal (one amino acid insertion) and therefore does not conflict with other benign lines of evidence. Therefore, in summary, the c.1487-5G>A variant in TCF4 is classified as benign based on the ACMG/AMP criteria (BA1, BS2).

PP3

The computational splicing predictor SpliceAI gives a score of 1 for acceptor loss, predicting that the variant disrupts the acceptor splice site of intron 16 of TCF4 (PP3). However, the resulting protein impact is minimal (one amino acid insertion) and therefore does not conflict with other benign lines of evidence.

BA1

BS2

The c.1487-5G>A variant is observed in at least 2 unaffected individuals (Internal database - Ambry) (BS2).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.