rs12186731

Variant names:

• chr5-157110905-C-T
• rs12186731
• ENST00000696899.1:c.-264-1658G>A

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-293-3943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,878 control chromosomes in the GnomAD database, including 1,110 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 0.11 (1110 hom., cov: 32)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 3 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
• HAVCR2-related cancer predisposition

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000254246 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524219.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000696899.1		c.-264-1658G>A		intron	N/A	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.-4-1918G>A		intron	N/A	ENSP00000523303.1
	HAVCR2	ENST00000524219.2	TSL:4	c.-293-3943G>A		intron	N/A	ENSP00000430328.2	E5RFR4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16536 AN: 151760 Hom.: 1112 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0918

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.109 AC: 16532 AN: 151878 Hom.: 1110 Cov.: 32 AF XY: 0.112 AC XY: 8300 AN XY: 74234

African (AFR) AF: 0.0358 AC: 1484 AN: 41434

American (AMR) AF: 0.116 AC: 1765 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0918 AC: 318 AN: 3464

East Asian (EAS) AF: 0.175 AC: 897 AN: 5128

South Asian (SAS) AF: 0.190 AC: 914 AN: 4804

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10562

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9241 AN: 67918

Other (OTH) AF: 0.109 AC: 229 AN: 2108

Alfa AF: 0.123 Hom.: 170

Bravo AF: 0.100

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs12186731; hg19: chr5-156537916;