ENST00000696899.1:c.-264-1252G>T

Variant names:

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

Variant summary

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

The ENST00000696899.1(HAVCR2):​c.-264-1252G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 151,832 control chromosomes in the GnomAD database, including 433 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 0.061 (433 hom., cov: 32)
• Consequence: HAVCR2 ENST00000696899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ENSG00000254246 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000696899.1	c.-264-1252G>T		intron_variant	Intron 1 of 7			ENSP00000512960.1
HAVCR2	ENST00000524219.2	c.-293-3537G>T		intron_variant	Intron 1 of 6	4		ENSP00000430328.2
ENSG00000254246	ENST00000517708.1	n.148-4274C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9267 AN: 151714 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0612 AC: 9297 AN: 151832 Hom.: 433 Cov.: 32 AF XY: 0.0643 AC XY: 4774 AN XY: 74190

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0564

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0515

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0225 Hom.: 6

Bravo AF: 0.0659

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10053538; hg19: chr5-156537510;