rs10213865

Positions:

• chr5-35857748-A-C
• chr5-35857748-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002185.5(IL7R):​c.82+689A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,006 control chromosomes in the GnomAD database, including 4,793 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4793 hom., cov: 31)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.82+689A>C		intron_variant		ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.82+689A>C		intron_variant		1	NM_002185.5	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37358 AN: 151888 Hom.: 4792 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37384 AN: 152006 Hom.: 4793 Cov.: 31 AF XY: 0.248 AC XY: 18433 AN XY: 74292

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.216

Alfa AF: 0.157 Hom.: 373

Bravo AF: 0.233

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.37

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: rs10213865; hg19: chr5-35857850;