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.1241C>T (p.Thr414Met)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA160123

134536 (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: d5b9112d-d56d-4e07-8713-01a5d04b0d59

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_002185.5:c.1241C>T

NM_002185.5(IL7R):c.1241C>T (p.Thr414Met)

NC_000005.10:g.35876347C>T

CM000667.2:g.35876347C>T

NC_000005.9:g.35876449C>T

CM000667.1:g.35876449C>T

NC_000005.8:g.35912206C>T

NG_009567.1:g.24459C>T

ENST00000303115.8:c.1241C>T

ENST00000303115.7:c.1241C>T

ENST00000505093.1:c.556C>T

ENST00000505875.1:n.539C>T

ENST00000514217.5:c.*435C>T

NM_002185.3:c.1241C>T

NR_120485.1:n.1081C>T

NM_002185.4:c.1241C>T

NR_120485.2:n.1107C>T

NR_120485.3:n.1065C>T

Benign

BS2_Supporting BA1

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 NM_002185.5(IL7R):c.1241C>T (p.Thr414Met) missense variant occurs at a frequency too high for the disease. The filtering allele frequency based on the South Asian population (upper bound of 95% CI of 1076/30502 observed alleles) is 0.03353 in gnomAD v2.1.1, which is above the SCID-VCEP BA1 threshold (>0.00566). Also, 46 adult homozygous individuals with this variant are present in gnomAD v2.1.1 (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 and BS2_Supporting (SCID VCEP specifications version 1.0).

BS2_Supporting

46 adult homozygous individuals with this variant are present in gnomAD v2.1.1 (South Asian n=28, East Asian n=12, European Finnish n=1, European Non-Finnish n=4, and Other n=1)(BS2_Supporting).

BA1

The filtering allele frequency based on the South Asian population (upper bound of 95% CI of 1076/30502 observed alleles) is 0.03353 in gnomAD v2.1.1 which is above the SCID-VCEP threshold (>0.00566) and therefore meets this criterion (BA1).

Curation History

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