rs4704846

Positions:

• chr5-157086333-G-A
• chr5-157086333-G-C
• chr5-157086333-G-T

Variant summary

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

The NM_032782.5(HAVCR2):​c.*769C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,202 control chromosomes in the GnomAD database, including 48,581 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 0.79 (48581 hom., cov: 33)
  • Exomes 𝑓: 0.81 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: HAVCR2 NM_032782.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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=-0.91).
• 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	UniProt
HAVCR2	NM_032782.5	c.*769C>T		3_prime_UTR_variant	7/7	ENST00000307851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR2	ENST00000307851.9	c.*769C>T		3_prime_UTR_variant	7/7	1	NM_032782.5	P2

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120867 AN: 152084 Hom.: 48548 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.806

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.813 AC: 26 AN: 32 Hom.: 11 Cov.: 0 AF XY: 0.818 AC XY: 18 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.821

GnomAD4 genome AF: 0.795 AC: 120952 AN: 152202 Hom.: 48581 Cov.: 33 AF XY: 0.803 AC XY: 59776 AN XY: 74416

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.807

Alfa AF: 0.804 Hom.: 19300

Bravo AF: 0.791

Asia WGS AF: 0.945 AC: 3286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.35

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: rs4704846; hg19: chr5-156513344;