rs41297579

Positions:

• chr5-157059397-C-T

Variant summary

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

The ENST00000699093.1(HAVCR1):​c.-12-1442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,158 control chromosomes in the GnomAD database, including 1,914 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 0.15 (1914 hom., cov: 33)
• Consequence: HAVCR1 ENST00000699093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR1	XM_024446020.2	c.-136-1318G>A		intron_variant			XP_024301788.1
HAVCR1	XM_024446021.2	c.-133-1321G>A		intron_variant			XP_024301789.1
HAVCR1	XM_024446023.2	c.-12-1442G>A		intron_variant			XP_024301791.1
HAVCR1	XM_047417097.1	c.-12-1442G>A		intron_variant			XP_047273053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000699093.1	c.-12-1442G>A		intron_variant				ENSP00000514125.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22602 AN: 152040 Hom.: 1910 Cov.: 33

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.149 AC: 22622 AN: 152158 Hom.: 1914 Cov.: 33 AF XY: 0.152 AC XY: 11272 AN XY: 74382

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.156

Alfa AF: 0.136 Hom.: 232

Bravo AF: 0.153

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41297579; hg19: chr5-156486408;