5-157110749-A-C

Variant names:

• chr5-157110749-A-C
• rs10061463
• ENST00000696899.1:c.-264-1502T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696899.1(HAVCR2):​c.-264-1502T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,162 control chromosomes in the GnomAD database, including 56,534 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 0.86 (56534 hom., cov: 32)
• Consequence: HAVCR2 ENST00000696899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 6 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

ENSG00000254246 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696899.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000696899.1		c.-264-1502T>G		intron	N/A	ENSP00000512960.1
	HAVCR2	ENST00000524219.2	TSL:4	c.-293-3787T>G		intron	N/A	ENSP00000430328.2
	ENSG00000254246	ENST00000517708.1	TSL:3	n.148-4024A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130895 AN: 152044 Hom.: 56480 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.861 AC: 131009 AN: 152162 Hom.: 56534 Cov.: 32 AF XY: 0.867 AC XY: 64508 AN XY: 74382

African (AFR) AF: 0.879 AC: 36479 AN: 41482

American (AMR) AF: 0.902 AC: 13776 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3091 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5123 AN: 5190

South Asian (SAS) AF: 0.953 AC: 4593 AN: 4820

European-Finnish (FIN) AF: 0.859 AC: 9092 AN: 10590

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55974 AN: 68018

Other (OTH) AF: 0.862 AC: 1820 AN: 2112

Alfa AF: 0.842 Hom.: 19852

Bravo AF: 0.865

Asia WGS AF: 0.962 AC: 3345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.58
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs10061463; hg19: chr5-156537760;