ENST00000699093.1:c.-12-1442G>A

Variant names:

• chr5-157059397-C-T
• rs41297579
• ENST00000699093.1:c.-12-1442G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HAVCR1	XM_024446020.2	c.-136-1318G>A		intron_variant	Intron 1 of 7		XP_024301788.1
HAVCR1	XM_024446021.2	c.-133-1321G>A		intron_variant	Intron 1 of 7		XP_024301789.1
HAVCR1	XM_024446023.2	c.-12-1442G>A		intron_variant	Intron 1 of 7		XP_024301791.1
HAVCR1	XM_047417097.1	c.-12-1442G>A		intron_variant	Intron 1 of 8		XP_047273053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000699093.1	c.-12-1442G>A		intron_variant	Intron 1 of 6			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

African (AFR) AF: 0.0859 AC: 3567 AN: 41526

American (AMR) AF: 0.235 AC: 3593 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.138 AC: 715 AN: 5176

South Asian (SAS) AF: 0.146 AC: 706 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2135 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10780 AN: 68010

Other (OTH) AF: 0.156 AC: 329 AN: 2110

Alfa AF: 0.151 Hom.: 2727

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
PhyloP100		-2.1
PromoterAI		0.0088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs41297579; hg19: chr5-156486408;