rs10941267

chr5-35869716-G-Achr5-35869716-G-T

Variant summary

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

The NM_002185.5(IL7R):c.380-1340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,044 control chromosomes in the GnomAD database, including 37,128 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 0.69 (37128 hom., cov: 31)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL7R	NM_002185.5	c.380-1340G>A		intron_variant		ENST00000303115.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000303115.8	c.380-1340G>A		intron_variant		1	NM_002185.5	P1
IL7R	ENST00000506850.5	c.380-1340G>A		intron_variant		2
IL7R	ENST00000514217.5	c.380-1340G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105263 AN: 151924 Hom.: 37109 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.693 AC: 105326 AN: 152044 Hom.: 37128 Cov.: 31 AF XY: 0.689 AC XY: 51201 AN XY: 74316

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.674

Alfa AF: 0.651 Hom.: 6660

Bravo AF: 0.687

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.54
Dann	Benign	0.60

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: rs10941267; hg19: chr5-35869818;