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_002185.5(IL7R):c.495C>T (p.His165=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA291241

137585 (ClinVar)

Gene: IL7R

Condition: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 863300c7-52e7-465e-b50b-3fd173b5c690

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_002185.5:c.495C>T

NM_002185.5(IL7R):c.495C>T (p.His165=)

NC_000005.10:g.35871171C>T

CM000667.2:g.35871171C>T

NC_000005.9:g.35871273C>T

CM000667.1:g.35871273C>T

NC_000005.8:g.35907030C>T

NG_009567.1:g.19283C>T

ENST00000303115.8:c.495C>T

ENST00000303115.7:c.495C>T

ENST00000506850.5:c.495C>T

ENST00000514217.5:c.495C>T

NM_002185.3:c.495C>T

NR_120485.1:n.598C>T

NM_002185.4:c.495C>T

NR_120485.2:n.624C>T

NR_120485.3:n.582C>T

Benign

BS2_Supporting BA1 BP7

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IL7R Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The c.495C>T (p.His165=) variant (NM_002185.5) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7). The filtering allele frequency (the lower threshold of the 95% CI of 5398/35384) of the c.495C>T variant in IL7R is 0.1491 for Latino/Admixed American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 2363 homozygous individuals were reported (BS2_Supporting is met). In summary, this variant is classified as Benign for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): BP7, BA1, and BS2_Supporting.

BS2_Supporting

There are 2363 homozygous individuals reported (gnomAD v.2.1.1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 5398/35384) of the c.495C>T variant in IL7R is 0.1491 for Latino/Admixed American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 2363 homozygous individuals were reported (BS2_Supporting is met).

BP7

The c.495C>T (p.His165=) variant (NM_002185.5) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7).

Curation History

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