rs418899

Variant names:

• chr5-157127653-G-A
• rs418899
• ENST00000524219.2:c.-294+15167C>T

Your query was ambiguous. Multiple possible variants found:

• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000524219.2	c.-294+15167C>T		intron_variant	Intron 1 of 6	4		ENSP00000430328.2

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;