rs10063294

Variant names:

• chr5-35877403-G-A
• rs10063294
• NM_002185.5:c.*917G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-35877403-G-A
• chr5-35877403-G-C
• chr5-35877403-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002185.5(IL7R):​c.*917G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 232,890 control chromosomes in the GnomAD database, including 37,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26489 hom., cov: 31)
  • Exomes 𝑓: 0.50 (10571 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.218
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-35877403-G-A is Benign according to our data. Variant chr5-35877403-G-A is described in ClinVar as Benign. ClinVar VariationId is 353284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.*917G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.*917G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87742 AN: 151914 Hom.: 26464 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.501 AC: 40524 AN: 80858 Hom.: 10571 Cov.: 0 AF XY: 0.501 AC XY: 18612 AN XY: 37160

African (AFR) AF: 0.744 AC: 2895 AN: 3890

American (AMR) AF: 0.408 AC: 1019 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 2622 AN: 5112

East Asian (EAS) AF: 0.306 AC: 3484 AN: 11402

South Asian (SAS) AF: 0.454 AC: 318 AN: 700

European-Finnish (FIN) AF: 0.638 AC: 37 AN: 58

Middle Eastern (MID) AF: 0.494 AC: 243 AN: 492

European-Non Finnish (NFE) AF: 0.528 AC: 26383 AN: 49944

Other (OTH) AF: 0.521 AC: 3523 AN: 6760

GnomAD4 genome AF: 0.578 AC: 87813 AN: 152032 Hom.: 26489 Cov.: 31 AF XY: 0.576 AC XY: 42768 AN XY: 74306

African (AFR) AF: 0.746 AC: 30924 AN: 41474

American (AMR) AF: 0.431 AC: 6581 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1422 AN: 5178

South Asian (SAS) AF: 0.448 AC: 2156 AN: 4808

European-Finnish (FIN) AF: 0.636 AC: 6712 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36405 AN: 67964

Other (OTH) AF: 0.529 AC: 1114 AN: 2106

Alfa AF: 0.540 Hom.: 42231

Bravo AF: 0.569

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Immunodeficiency 104 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.84
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10063294; hg19: chr5-35877505;