rs9292618

Positions:

• chr5-35878410-G-A

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.*1924G>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 0.132 in 232,966 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1318 hom., cov: 33)
  • Exomes 𝑓: 0.13 (748 hom.)
• Consequence: IL7R NM_002185.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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=-0.95).
• BP6: Variant 5-35878410-G-A is Benign according to our data. Variant chr5-35878410-G-A is described in ClinVar as [Benign]. Clinvar id is 353301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.*1924G>A		3_prime_UTR_variant	8/8	ENST00000303115.8
IL7R	NM_001410734.1	c.*2421G>A		3_prime_UTR_variant	7/7
IL7R	NR_120485.3	n.3128G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.*1924G>A		3_prime_UTR_variant	8/8	1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19948 AN: 152060 Hom.: 1318 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.134 AC: 10808 AN: 80788 Hom.: 748 Cov.: 0 AF XY: 0.134 AC XY: 4968 AN XY: 37124

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.131 AC: 19940 AN: 152178 Hom.: 1318 Cov.: 33 AF XY: 0.128 AC XY: 9513 AN XY: 74394

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.144

Alfa AF: 0.134 Hom.: 213

Bravo AF: 0.139

Asia WGS AF: 0.108 AC: 374 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 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	-0.95
CADD	Benign	0.075
DANN	Benign	0.41

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: rs9292618; hg19: chr5-35878512;