rs6555820

chr5-157045138-C-Achr5-157045138-C-T

Variant summary

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

The NM_001173393.3(HAVCR1):c.782-2456G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,730 control chromosomes in the GnomAD database, including 18,885 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 0.50 (18885 hom., cov: 31)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

HAVCR1 (HGNC:17866): (hepatitis A virus cellular receptor 1) The protein encoded by this gene is a membrane receptor for both human hepatitis A virus (HHAV) and TIMD4. The encoded protein may be involved in the moderation of asthma and allergic diseases. The reference genome represents an allele that retains a MTTVP amino acid segment that confers protection against atopy in HHAV seropositive individuals. The protein is a receptor for multiple other viruses, including Ebola virus, Marburg virus, Dengue virus, and Zika virus and is a possible entry factor for SARS-CoV-2 and other coronaviruses. [provided by RefSeq, Sep 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.782-2456G>T		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.782-2456G>T		intron_variant		1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75213 AN: 151612 Hom.: 18874 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.496 AC: 75263 AN: 151730 Hom.: 18885 Cov.: 31 AF XY: 0.492 AC XY: 36489 AN XY: 74096

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.527

Alfa AF: 0.373 Hom.: 1337

Bravo AF: 0.507

Asia WGS AF: 0.415 AC: 1447 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.60
Dann	Benign	0.18

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: rs6555820; hg19: chr5-156472149;