5-157110499-C-T

Variant names:

• chr5-157110499-C-T
• rs10053538
• ENST00000696899.1:c.-264-1252G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000524219.2(HAVCR2):​c.-293-3537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 151,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00024 (0 hom., cov: 32)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 47 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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.-264-1252G>A		intron	N/A	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.-4-1512G>A		intron	N/A	ENSP00000523303.1
	HAVCR2	ENST00000524219.2	TSL:4	c.-293-3537G>A		intron	N/A	ENSP00000430328.2	E5RFR4

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151734 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000486

Gnomad OTH AF: 0.00145

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

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151734 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74070

African (AFR) AF: 0.00 AC: 0 AN: 41296

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000486 AC: 33 AN: 67960

Other (OTH) AF: 0.00145 AC: 3 AN: 2066

Alfa AF: 0.0000543 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		0.21

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10053538;

hg19: chr5-156537510;