rs2172749

Positions:

• chr5-35855162-G-C
• chr5-35855162-G-T

Variant summary

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

The ENST00000508941.5(IL7R):​c.-139-870G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,056 control chromosomes in the GnomAD database, including 38,842 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 0.70 (38842 hom., cov: 32)
• Consequence: IL7R ENST00000508941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL7R	ENST00000508941.5	c.-139-870G>C		intron_variant		4
IL7R	ENST00000511031.1	n.216+2224G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106995 AN: 151938 Hom.: 38818 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.704 AC: 107067 AN: 152056 Hom.: 38842 Cov.: 32 AF XY: 0.698 AC XY: 51863 AN XY: 74306

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.673

Alfa AF: 0.589 Hom.: 1671

Bravo AF: 0.704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2172749; hg19: chr5-35855264;