rs13170556

chr5-157095577-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR2	NM_032782.5	c.523-118A>G		intron_variant		ENST00000307851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000307851.9	c.523-118A>G		intron_variant		1	NM_032782.5	P2

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

Gnomad4 AFR exome AF: 0.0861

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.147

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

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.127

Alfa AF: 0.143 Hom.: 355

Bravo AF: 0.125

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.6
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs13170556; hg19: chr5-156522588;