5-157061892-T-C

Position:

• chr5-157061892-T-C

Variant summary

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

The ENST00000699093.1(HAVCR1):​c.-12-3937A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,932 control chromosomes in the GnomAD database, including 29,911 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 0.63 (29911 hom., cov: 31)
• Consequence: HAVCR1 ENST00000699093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	XM_024446020.2	c.-136-3813A>G		intron_variant
HAVCR1	XM_024446021.2	c.-133-3816A>G		intron_variant
HAVCR1	XM_024446023.2	c.-12-3937A>G		intron_variant
HAVCR1	XM_047417097.1	c.-12-3937A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000699093.1	c.-12-3937A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94929 AN: 151814 Hom.: 29899 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.625 AC: 94986 AN: 151932 Hom.: 29911 Cov.: 31 AF XY: 0.627 AC XY: 46576 AN XY: 74264

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.630

Alfa AF: 0.630 Hom.: 59636

Bravo AF: 0.624

Asia WGS AF: 0.784 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.080
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6873777; hg19: chr5-156488903; COSMIC: COSV59398764;