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

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

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 id 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
IL7R	NM_001410734.1	c.*1414G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001397663.1
IL7R	NR_120485.3	n.2121G>A		non_coding_transcript_exon_variant	Exon 6 of 6

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

Gnomad4 AFR exome AF: 0.744 AC: 2895 AN: 3890

Gnomad4 AMR exome AF: 0.408 AC: 1019 AN: 2500

Gnomad4 ASJ exome AF: 0.513 AC: 2622 AN: 5112

Gnomad4 EAS exome AF: 0.306 AC: 3484 AN: 11402

Gnomad4 SAS exome AF: 0.454 AC: 318 AN: 700

Gnomad4 FIN exome AF: 0.638 AC: 37 AN: 58

Gnomad4 NFE exome AF: 0.528 AC: 26383 AN: 49944

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.746 AC: 0.745624 AN: 0.745624

Gnomad4 AMR AF: 0.431 AC: 0.430694 AN: 0.430694

Gnomad4 ASJ AF: 0.507 AC: 0.50692 AN: 0.50692

Gnomad4 EAS AF: 0.275 AC: 0.274623 AN: 0.274623

Gnomad4 SAS AF: 0.448 AC: 0.448419 AN: 0.448419

Gnomad4 FIN AF: 0.636 AC: 0.636088 AN: 0.636088

Gnomad4 NFE AF: 0.536 AC: 0.535651 AN: 0.535651

Gnomad4 OTH AF: 0.529 AC: 0.528965 AN: 0.528965

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs10063294; hg19: chr5-35877505;