rs431620

Variant names:

• chr5-157119617-C-G
• rs431620
• ENST00000524219.2:c.-293-12655G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

HAVCR2 Gene-Disease associations (from GenCC):

• subcutaneous panniculitis-like T-cell lymphoma

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000524219.2	c.-293-12655G>C		intron_variant	Intron 1 of 6	4		ENSP00000430328.2

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

African (AFR) AF: 0.794 AC: 32948 AN: 41502

American (AMR) AF: 0.877 AC: 13396 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3037 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5100 AN: 5178

South Asian (SAS) AF: 0.948 AC: 4578 AN: 4828

European-Finnish (FIN) AF: 0.850 AC: 9005 AN: 10588

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54780 AN: 68000

Other (OTH) AF: 0.832 AC: 1753 AN: 2108

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
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs431620; hg19: chr5-156546628;