rs418899

Positions:

• chr5-157127653-G-A
• chr5-157127653-G-C
• chr5-157127653-G-T

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-294+15167C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 150,984 control chromosomes in the GnomAD database, including 10,642 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 0.36 (10642 hom., cov: 32)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000524219.2	c.-294+15167C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53607 AN: 150876 Hom.: 10607 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.356 AC: 53683 AN: 150984 Hom.: 10642 Cov.: 32 AF XY: 0.350 AC XY: 25788 AN XY: 73610

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.333

Alfa AF: 0.318 Hom.: 1654

Bravo AF: 0.361

Asia WGS AF: 0.235 AC: 819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs418899; hg19: chr5-156554664;