rs10491434

chr5-35877812-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002185.5(IL7R):c.*1326A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 232,966 control chromosomes in the GnomAD database, including 10,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8129 hom., cov: 32)
  • Exomes 𝑓: 0.25 (2757 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-35877812-A-G is Benign according to our data. Variant chr5-35877812-A-G is described in ClinVar as [Benign]. Clinvar id is 353290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.*1326A>G		3_prime_UTR_variant	8/8	ENST00000303115.8
IL7R	NM_001410734.1	c.*1823A>G		3_prime_UTR_variant	7/7
IL7R	NR_120485.3	n.2530A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.*1326A>G		3_prime_UTR_variant	8/8	1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47107 AN: 151884 Hom.: 8126 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.248 AC: 20065 AN: 80964 Hom.: 2757 Cov.: 0 AF XY: 0.247 AC XY: 9208 AN XY: 37210

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.0757

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.310 AC: 47131 AN: 152002 Hom.: 8129 Cov.: 32 AF XY: 0.307 AC XY: 22822 AN XY: 74292

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.303

Alfa AF: 0.277 Hom.: 3635

Bravo AF: 0.312

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 104 Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.3
Dann	Benign	0.72

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: rs10491434; hg19: chr5-35877914;