rs431620

Positions:

• chr5-157119617-C-G

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-293-12655G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,160 control chromosomes in the GnomAD database, including 52,062 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 0.83 (52062 hom., cov: 31)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

Genes affected

HAVCR2 (HGNC:18437): (hepatitis A virus cellular receptor 2) The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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
HAVCR2	ENST00000524219.2	c.-293-12655G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125558 AN: 152042 Hom.: 52026 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.826 AC: 125648 AN: 152160 Hom.: 52062 Cov.: 31 AF XY: 0.833 AC XY: 61977 AN XY: 74378

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.832

Alfa AF: 0.804 Hom.: 6124

Bravo AF: 0.826

Asia WGS AF: 0.952 AC: 3311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs431620; hg19: chr5-156546628;