rs13170556

Variant names:

• chr5-157095577-T-C
• rs13170556
• NM_032782.5:c.523-118A>G

Variant summary

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

The NM_032782.5(HAVCR2):​c.523-118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,066,734 control chromosomes in the GnomAD database, including 12,495 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 0.13 (1405 hom., cov: 31)
  • Exomes 𝑓: 0.15 (11090 hom.)
• Consequence: HAVCR2 NM_032782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853
• Publications: 7 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032782.5. 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
	HAVCR2	NM_032782.5	MANE Select	c.523-118A>G		intron	N/A	NP_116171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAVCR2	ENST00000307851.9	TSL:1 MANE Select	c.523-118A>G		intron	N/A	ENSP00000312002.4
	HAVCR2	ENST00000521665.2	TSL:1	c.172-118A>G		intron	N/A	ENSP00000513314.1
	HAVCR2	ENST00000696899.1		c.523-118A>G		intron	N/A	ENSP00000512960.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19946 AN: 152006 Hom.: 1405 Cov.: 31

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.152 AC: 139127 AN: 914610 Hom.: 11090 AF XY: 0.155 AC XY: 72269 AN XY: 465458

African (AFR) AF: 0.0861 AC: 1896 AN: 22026

American (AMR) AF: 0.134 AC: 4233 AN: 31500

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2046 AN: 18826

East Asian (EAS) AF: 0.199 AC: 6893 AN: 34596

South Asian (SAS) AF: 0.223 AC: 13970 AN: 62644

European-Finnish (FIN) AF: 0.149 AC: 5625 AN: 37724

Middle Eastern (MID) AF: 0.165 AC: 601 AN: 3638

European-Non Finnish (NFE) AF: 0.148 AC: 97708 AN: 661682

Other (OTH) AF: 0.147 AC: 6155 AN: 41974

GnomAD4 genome AF: 0.131 AC: 19956 AN: 152124 Hom.: 1405 Cov.: 31 AF XY: 0.133 AC XY: 9912 AN XY: 74366

African (AFR) AF: 0.0856 AC: 3555 AN: 41512

American (AMR) AF: 0.130 AC: 1983 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.173 AC: 896 AN: 5180

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10574

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10122 AN: 67986

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.141 Hom.: 2625

Bravo AF: 0.125

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs13170556; hg19: chr5-156522588;