rs11567764

chr5-35873503-G-Achr5-35873503-G-Cchr5-35873503-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002185.5(IL7R):c.561G>A(p.Lys187=) 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:4
• Conservation: PhyloP100: 0.798

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 137587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-35873503-G-A is described in Lovd as [Likely_benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.561G>A	p.Lys187=	synonymous_variant	5/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.561G>A	p.Lys187=	synonymous_variant	5/8	1	NM_002185.5	P1

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

GnomAD3 exomes AF: 0.00953 AC: 2390 AN: 250744 Hom.: 137 AF XY: 0.00674 AC XY: 914 AN XY: 135522

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 SAS exome AF: 0.000294

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

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00655

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00881

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

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.00640 Hom.: 39

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 104 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2013

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. -

IL7R-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2019

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.2
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

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