rs149235072

Positions:

• chr5-35860922-G-A
• chr5-35860922-G-C
• chr5-35860922-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002185.5(IL7R):​c.153G>A​(p.Ser51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,613,122 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (64 hom.)
• Consequence: IL7R NM_002185.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.129

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=-0.81).
• BP6: Variant 5-35860922-G-A is Benign according to our data. Variant chr5-35860922-G-A is described in ClinVar as [Benign]. Clinvar id is 353261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-35860922-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.129 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00135 (205/152240) while in subpopulation SAS AF= 0.0327 (158/4826). AF 95% confidence interval is 0.0286. There are 5 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.153G>A	p.Ser51=	synonymous_variant	2/8	ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.153G>A	p.Ser51=	synonymous_variant	2/8	1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 202 AN: 152122 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00385 AC: 968 AN: 251152 Hom.: 18 AF XY: 0.00521 AC XY: 707 AN XY: 135710

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0296

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00217 AC: 3177 AN: 1460882 Hom.: 64 Cov.: 30 AF XY: 0.00294 AC XY: 2140 AN XY: 726840

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0285

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000464

Gnomad4 OTH exome AF: 0.00247

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152240 Hom.: 5 Cov.: 32 AF XY: 0.00192 AC XY: 143 AN XY: 74426

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000376 Hom.: 0

Bravo AF: 0.000536

Asia WGS AF: 0.0120 AC: 42 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.45

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: rs149235072; hg19: chr5-35861024; COSMIC: COSV57409062;