rs10515746

Positions:

• chr5-157109557-A-C
• chr5-157109557-A-T

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-293-2595T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,592 control chromosomes in the GnomAD database, including 48,984 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 0.80 (48798 hom., cov: 31)
  • Exomes 𝑓: 0.84 (186 hom.)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.157109557A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000696899.1	c.-264-310T>G		intron_variant				ENSP00000512960.1
HAVCR2	ENST00000524219.2	c.-293-2595T>G		intron_variant		4		ENSP00000430328.2
HAVCR2	ENST00000696901.1	n.-574T>G		non_coding_transcript_exon_variant	1/5			ENSP00000512962.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121180 AN: 151956 Hom.: 48762 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.840 AC: 435 AN: 518 Hom.: 186 Cov.: 0 AF XY: 0.844 AC XY: 211 AN XY: 250

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.902

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.875

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.797 AC: 121269 AN: 152074 Hom.: 48798 Cov.: 31 AF XY: 0.805 AC XY: 59854 AN XY: 74322

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.808

Alfa AF: 0.732 Hom.: 2507

Bravo AF: 0.793

Asia WGS AF: 0.941 AC: 3274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10515746; hg19: chr5-156536568;