ENST00000524219.2:c.-294+12985A>C

Variant names:

• chr5-157129835-T-G
• rs246879
• ENST00000524219.2:c.-294+12985A>C

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-294+12985A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,154 control chromosomes in the GnomAD database, including 1,168 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 0.12 (1168 hom., cov: 31)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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	ENST00000524219.2	TSL:4	c.-294+12985A>C		intron	N/A	ENSP00000430328.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18167 AN: 152038 Hom.: 1169 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.119 AC: 18175 AN: 152154 Hom.: 1168 Cov.: 31 AF XY: 0.115 AC XY: 8522 AN XY: 74410

African (AFR) AF: 0.141 AC: 5858 AN: 41492

American (AMR) AF: 0.0874 AC: 1336 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3466

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5184

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4826

European-Finnish (FIN) AF: 0.0904 AC: 957 AN: 10592

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9032 AN: 67988

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.124 Hom.: 670

Bravo AF: 0.121

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.50
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs246879; hg19: chr5-156556846;