rs4869492

Variant names:

• chr5-35855308-T-C
• rs4869492
• ENST00000508941.5:c.-139-724T>C

Variant summary

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

The ENST00000508941.5(IL7R):​c.-139-724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,204 control chromosomes in the GnomAD database, including 1,247 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 0.13 (1247 hom., cov: 32)
• Consequence: IL7R ENST00000508941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 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.-139-724T>C		intron_variant	Intron 1 of 3	4		ENSP00000426426.1
IL7R	ENST00000511031.1	n.216+2370T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19491 AN: 152086 Hom.: 1247 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.128 AC: 19481 AN: 152204 Hom.: 1247 Cov.: 32 AF XY: 0.125 AC XY: 9320 AN XY: 74412

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.140

Alfa AF: 0.134 Hom.: 1343

Bravo AF: 0.136

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4869492; hg19: chr5-35855410;