5-35871171-C-T

Position:

chr5-35871171-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BS2_SupportingBA1

This summary comes from the ClinGen Evidence Repository: 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA291241/MONDO:0012163/119

Frequency

Genomes: 𝑓 0.13 ( 1327 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13845 hom. )

Consequence

IL7R
NM_002185.5 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:7

Conservation

PhyloP100: -0.446

Variant links:

Genes affected

IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]

IL7R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BS2

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL7R	NM_002185.5 linkuse as main transcript	c.495C>T	p.His165=	synonymous_variant	4/8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8 linkuse as main transcript	c.495C>T	p.His165=	synonymous_variant	4/8	1	NM_002185.5	ENSP00000306157	P1	P16871-1
IL7R	ENST00000506850.5 linkuse as main transcript	c.495C>T	p.His165=	synonymous_variant	4/6	2		ENSP00000421207		P16871-3
IL7R	ENST00000514217.5 linkuse as main transcript	c.495C>T	p.His165=	synonymous_variant, NMD_transcript_variant	4/6	2		ENSP00000427688

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

19986

AN:

151976

Hom.:

1327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0632

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.127

AC:

31804

AN:

251042

Hom.:

2132

AF XY:

0.122

AC XY:

16508

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.134

AC:

195901

AN:

1457346

Hom.:

13845

Cov.:

AF XY:

0.132

AC XY:

95373

AN XY:

725238

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.0614

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.131

AC:

19978

AN:

152094

Hom.:

1327

Cov.:

AF XY:

0.128

AC XY:

9523

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0624

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.137

Hom.:

1201

Bravo

AF:

0.139

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.139

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Immunodeficiency 104

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, reviewed by expert panel	curation	ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	Nov 14, 2023	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.5

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over