rs12186731

Positions:

• chr5-157110905-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517708.1(ENSG00000254246):​n.148-3868C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 151,878 control chromosomes in the GnomAD database, including 1,110 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 0.11 (1110 hom., cov: 32)
• Consequence: ENST00000517708.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

Genes affected

(HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000517708.1	n.148-3868C>T		intron_variant, non_coding_transcript_variant		3
HAVCR2	ENST00000524219.2	c.-293-3943G>A		intron_variant		4		ENSP00000430328
HAVCR2	ENST00000696899.1	c.-264-1658G>A		intron_variant				ENSP00000512960	P2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16536 AN: 151760 Hom.: 1112 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0918

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.109 AC: 16532 AN: 151878 Hom.: 1110 Cov.: 32 AF XY: 0.112 AC XY: 8300 AN XY: 74234

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0918

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.109

Alfa AF: 0.123 Hom.: 170

Bravo AF: 0.100

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12186731; hg19: chr5-156537916;