ENST00000696899.1:c.-264-618T>C

Variant names:

• chr5-157109865-A-G
• rs4704853
• ENST00000696899.1:c.-264-618T>C

Variant summary

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

The ENST00000696899.1(HAVCR2):​c.-264-618T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,054 control chromosomes in the GnomAD database, including 48,763 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 (48763 hom., cov: 31)
• Consequence: HAVCR2 ENST00000696899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.-264-618T>C		intron_variant	Intron 1 of 7			ENSP00000512960.1
HAVCR2	ENST00000524219.2	c.-293-2903T>C		intron_variant	Intron 1 of 6	4		ENSP00000430328.2
ENSG00000254246	ENST00000517708.1	n.148-4908A>G		intron_variant	Intron 1 of 1	3
HAVCR2	ENST00000696901.1	n.-882T>C		upstream_gene_variant				ENSP00000512962.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121108 AN: 151936 Hom.: 48727 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.797 AC: 121196 AN: 152054 Hom.: 48763 Cov.: 31 AF XY: 0.805 AC XY: 59848 AN XY: 74324

African (AFR) AF: 0.690 AC: 28605 AN: 41428

American (AMR) AF: 0.862 AC: 13160 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3053 AN: 3468

East Asian (EAS) AF: 0.987 AC: 5116 AN: 5184

South Asian (SAS) AF: 0.939 AC: 4519 AN: 4812

European-Finnish (FIN) AF: 0.853 AC: 9025 AN: 10580

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.808 AC: 54967 AN: 67996

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.785 Hom.: 6203

Bravo AF: 0.792

Asia WGS AF: 0.941 AC: 3273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.50
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs4704853; hg19: chr5-156536876;