5-157086171-G-C

Position:

• chr5-157086171-G-C

Variant summary

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

The NM_032782.5(HAVCR2):​c.*931C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,248 control chromosomes in the GnomAD database, including 53,401 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 0.84 (53379 hom., cov: 32)
  • Exomes 𝑓: 0.84 (22 hom.)
• Consequence: HAVCR2 NM_032782.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR2	NM_032782.5	c.*931C>G		3_prime_UTR_variant	7/7	ENST00000307851.9	NP_116171.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR2	ENST00000307851.9	c.*931C>G		3_prime_UTR_variant	7/7	1	NM_032782.5	ENSP00000312002	P2

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127139 AN: 152072 Hom.: 53329 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.845 AC: 49 AN: 58 Hom.: 22 Cov.: 0 AF XY: 0.850 AC XY: 34 AN XY: 40

Gnomad4 AFR exome AF: 0.833

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.836 AC: 127247 AN: 152190 Hom.: 53379 Cov.: 32 AF XY: 0.844 AC XY: 62825 AN XY: 74400

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.842

Alfa AF: 0.750 Hom.: 1568

Bravo AF: 0.836

Asia WGS AF: 0.960 AC: 3338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.6
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9313439; hg19: chr5-156513182;