rs10515746

Variant names:

• chr5-157109557-A-C
• rs10515746
• ENST00000696899.1:c.-264-310T>G

Your query was ambiguous. Multiple possible variants found:

• 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]

ENSG00000254246 (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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000696899.1	c.-264-310T>G		intron_variant	Intron 1 of 7			ENSP00000512960.1
HAVCR2	ENST00000524219.2	c.-293-2595T>G		intron_variant	Intron 1 of 6	4		ENSP00000430328.2
HAVCR2	ENST00000696901.1	n.-574T>G		non_coding_transcript_exon_variant	Exon 1 of 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;