NM_002185.5(IL7R):c.339A>C (p.Glu113Asp) AND Immunodeficiency 104

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jan 10, 2024
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000640071.14

Allele description [Variation Report for NM_002185.5(IL7R):c.339A>C (p.Glu113Asp)]

NM_002185.5(IL7R):c.339A>C (p.Glu113Asp)

Gene:

IL7R:interleukin 7 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p13.2

Genomic location:

Preferred name:

NM_002185.5(IL7R):c.339A>C (p.Glu113Asp)

Other names:

NM_002185.5(IL7R):c.339A>C; p.Glu113Asp

HGVS:

NC_000005.10:g.35867423A>C
NG_009567.1:g.15535A>C
NM_002185.5:c.339A>CMANE SELECT
NP_002176.2:p.Glu113Asp
LRG_74t1:c.339A>C
LRG_74:g.15535A>C
NC_000005.9:g.35867525A>C
NM_002185.2:c.339A>C
NM_002185.3:c.339A>C
NR_120485.3:n.426A>C

Protein change:

E113D

Links:

dbSNP: rs11567735

NCBI 1000 Genomes Browser:

rs11567735

Molecular consequence:

NM_002185.5:c.339A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_120485.3:n.426A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Immunodeficiency 104
Synonyms:: SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive; IMMUNODEFICIENCY 104, SEVERE COMBINED; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012163; MedGen: C5676890; OMIM: 608971

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761659	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Nov 13, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001529833	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 9, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004242293	ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen SCID ACMG Specifications IL7R V1.0.0)	Likely benign (Jan 10, 2024)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761659

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Nov 13, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001529833

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 9, 2018)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004242293

ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen SCID ACMG Specifications IL7R V1.0.0)

Likely benign
(Jan 10, 2024)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000761659.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV001529833.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV004242293.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

NM_002185.5(IL7R):c.339A>C is a missense variant predicted to cause substitution of Glutamic Acid by Aspartic Acid at amino acid 113 (p.Glu113Asp). The filtering allele frequency (the lower threshold of the 95% CI of 308/75016) of the c.339A>C variant in IL7R is 0.003481 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00126) for BS1, and therefore meets this criterion (BS1). To our knowledge, this variant has not been reported in the literature in individuals affected with IL7R-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as Likely Benign variant for autosomal recessive severe combined immunodeficiency due to IL7R deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BS1_met (VCEP specifications version 1).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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