rs11567764

Variant names:

• chr5-35873503-G-A
• rs11567764
• NM_002185.5:c.561G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-35873503-G-A
• chr5-35873503-G-C
• chr5-35873503-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002185.5(IL7R):​c.561G>A​(p.Lys187Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,613,958 control chromosomes in the GnomAD database, including 649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (318 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (331 hom.)
• Consequence: IL7R NM_002185.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.798
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-35873503-G-A is Benign according to our data. Variant chr5-35873503-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.798 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002185.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	NM_002185.5	MANE Select	c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 8	NP_002176.2
	IL7R	NM_001437964.1		c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 7	NP_001424893.1
	IL7R	NM_001410734.1		c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 7	NP_001397663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL7R	ENST00000303115.8	TSL:1 MANE Select	c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 8	ENSP00000306157.3
	IL7R	ENST00000506850.5	TSL:2	c.561G>A	p.Lys187Lys	synonymous	Exon 5 of 6	ENSP00000421207.1
	IL7R	ENST00000509668.1	TSL:5	n.303G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5468 AN: 152138 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0316

GnomAD2 exomes AF: 0.00953 AC: 2390 AN: 250744 AF XY: 0.00674

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.00593

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00379 AC: 5547 AN: 1461702 Hom.: 331 Cov.: 30 AF XY: 0.00324 AC XY: 2357 AN XY: 727166

African (AFR) AF: 0.134 AC: 4486 AN: 33436

American (AMR) AF: 0.00655 AC: 293 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5766

European-Non Finnish (NFE) AF: 0.000148 AC: 165 AN: 1111912

Other (OTH) AF: 0.00881 AC: 532 AN: 60384

GnomAD4 genome AF: 0.0361 AC: 5498 AN: 152256 Hom.: 318 Cov.: 32 AF XY: 0.0346 AC XY: 2573 AN XY: 74442

African (AFR) AF: 0.126 AC: 5216 AN: 41520

American (AMR) AF: 0.0118 AC: 181 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68038

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.00710 Hom.: 44

Bravo AF: 0.0416

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 104 Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Feb 14, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

IL7R-related disorder Benign:1

Jul 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		0.80
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11567764; hg19: chr5-35873605; COSMIC: COSV57406853;