rs7702919

chr5-157059580-T-C

Variant summary

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

The ENST00000699093.1(HAVCR1):c.-12-1625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,916 control chromosomes in the GnomAD database, including 25,850 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 0.57 (25850 hom., cov: 32)
• Consequence: HAVCR1 ENST00000699093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.93).
• 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.-136-1501A>G		intron_variant
HAVCR1	XM_024446021.2	c.-133-1504A>G		intron_variant
HAVCR1	XM_024446023.2	c.-12-1625A>G		intron_variant
HAVCR1	XM_047417097.1	c.-12-1625A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000699093.1	c.-12-1625A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86932 AN: 151798 Hom.: 25846 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.572 AC: 86961 AN: 151916 Hom.: 25850 Cov.: 32 AF XY: 0.575 AC XY: 42727 AN XY: 74254

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.593

Alfa AF: 0.594 Hom.: 3398

Bravo AF: 0.562

Asia WGS AF: 0.771 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.3
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7702919; hg19: chr5-156486591; COSMIC: COSV59398741;