5-35857075-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002185.5(IL7R):c.82+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,504,278 control chromosomes in the GnomAD database, including 335,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39202 hom., cov: 31)
  • Exomes 𝑓: 0.66 (295827 hom.)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.54

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-35857075-G-C is Benign according to our data. Variant chr5-35857075-G-C is described in ClinVar as [Benign]. Clinvar id is 258579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-35857075-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.82+16G>C		intron_variant		ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.82+16G>C		intron_variant		1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107499 AN: 151956 Hom.: 39184 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.678

GnomAD3 exomes AF: 0.627 AC: 155530 AN: 248058 Hom.: 50731 AF XY: 0.625 AC XY: 84011 AN XY: 134392

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.420

Gnomad SAS exome AF: 0.518

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.657 AC: 888434 AN: 1352202 Hom.: 295827 Cov.: 21 AF XY: 0.653 AC XY: 443204 AN XY: 678930

Gnomad4 AFR exome AF: 0.880

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.707 AC: 107565 AN: 152076 Hom.: 39202 Cov.: 31 AF XY: 0.702 AC XY: 52165 AN XY: 74322

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.676

Alfa AF: 0.625 Hom.: 3663

Bravo AF: 0.706

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Immunodeficiency 104 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.8
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1353252; hg19: chr5-35857177; COSMIC: COSV57406102;