rs2172749

Variant names:

• chr5-35855162-G-C
• rs2172749
• ENST00000508941.5:c.-139-870G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

IL7R Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000508941.5	c.-139-870G>C		intron_variant	Intron 1 of 3	4		ENSP00000426426.1
IL7R	ENST00000511031.1	n.216+2224G>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.871 AC: 36165 AN: 41510

American (AMR) AF: 0.573 AC: 8751 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2210 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2149 AN: 5164

South Asian (SAS) AF: 0.516 AC: 2480 AN: 4810

European-Finnish (FIN) AF: 0.710 AC: 7499 AN: 10562

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45483 AN: 67960

Other (OTH) AF: 0.673 AC: 1419 AN: 2110

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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2172749; hg19: chr5-35855264;