5-157109557-A-C

Variant names:

• chr5-157109557-A-C
• rs10515746
• ENST00000696899.1:c.-264-310T>G

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-293-2595T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,592 control chromosomes in the GnomAD database, including 48,984 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 (48798 hom., cov: 31)
  • Exomes 𝑓: 0.84 (186 hom.)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 72 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=-0.89).
• 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: 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.-264-310T>G		intron	N/A	ENSP00000512960.1	Q8TDQ0-1
	HAVCR2	ENST00000853244.1		c.-4-570T>G		intron	N/A	ENSP00000523303.1
	HAVCR2	ENST00000524219.2	TSL:4	c.-293-2595T>G		intron	N/A	ENSP00000430328.2	E5RFR4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121180 AN: 151956 Hom.: 48762 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.840 AC: 435 AN: 518 Hom.: 186 Cov.: 0 AF XY: 0.844 AC XY: 211 AN XY: 250

African (AFR) AF: 0.833 AC: 5 AN: 6

American (AMR) AF: 0.902 AC: 101 AN: 112

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AF: 0.875 AC: 21 AN: 24

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.812 AC: 281 AN: 346

Other (OTH) AF: 0.900 AC: 18 AN: 20

GnomAD4 genome AF: 0.797 AC: 121269 AN: 152074 Hom.: 48798 Cov.: 31 AF XY: 0.805 AC XY: 59854 AN XY: 74322

African (AFR) AF: 0.692 AC: 28692 AN: 41452

American (AMR) AF: 0.862 AC: 13164 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3054 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5104 AN: 5170

South Asian (SAS) AF: 0.940 AC: 4521 AN: 4810

European-Finnish (FIN) AF: 0.853 AC: 9022 AN: 10580

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54959 AN: 67998

Other (OTH) AF: 0.808 AC: 1709 AN: 2114

Alfa AF: 0.732 Hom.: 2507

Bravo AF: 0.793

Asia WGS AF: 0.941 AC: 3274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.54
PhyloP100		-0.24
PromoterAI		-0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10515746; hg19: chr5-156536568;