5-157129835-T-G

Variant names:

• chr5-157129835-T-G
• rs246879
• ENST00000524219.2:c.-294+12985A>C

Variant summary

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

The ENST00000524219.2(HAVCR2):​c.-294+12985A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,154 control chromosomes in the GnomAD database, including 1,168 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 0.12 (1168 hom., cov: 31)
• Consequence: HAVCR2 ENST00000524219.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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+12985A>C		intron_variant	Intron 1 of 6	4		ENSP00000430328.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18167 AN: 152038 Hom.: 1169 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.119 AC: 18175 AN: 152154 Hom.: 1168 Cov.: 31 AF XY: 0.115 AC XY: 8522 AN XY: 74410

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0874

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.125

Alfa AF: 0.124 Hom.: 583

Bravo AF: 0.121

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs246879; hg19: chr5-156556846;