ENST00000699093.1:c.-13+5217T>C

Variant names:

• chr5-157064142-A-G
• rs4704843
• ENST00000699093.1:c.-13+5217T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699093.1(HAVCR1):​c.-13+5217T>C 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 151,980 control chromosomes in the GnomAD database, including 29,942 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 (29942 hom., cov: 31)
• Consequence: HAVCR1 ENST00000699093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	XM_024446020.2	c.-137+5217T>C		intron_variant	Intron 1 of 7		XP_024301788.1
HAVCR1	XM_024446021.2	c.-134+5217T>C		intron_variant	Intron 1 of 7		XP_024301789.1
HAVCR1	XM_024446023.2	c.-13+5217T>C		intron_variant	Intron 1 of 7		XP_024301791.1
HAVCR1	XM_047417097.1	c.-13+5217T>C		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.-13+5217T>C		intron_variant	Intron 1 of 6			ENSP00000514125.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94970 AN: 151864 Hom.: 29929 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.625 AC: 95029 AN: 151980 Hom.: 29942 Cov.: 31 AF XY: 0.627 AC XY: 46604 AN XY: 74272

African (AFR) AF: 0.597 AC: 24769 AN: 41456

American (AMR) AF: 0.616 AC: 9398 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4377 AN: 5166

South Asian (SAS) AF: 0.782 AC: 3758 AN: 4804

European-Finnish (FIN) AF: 0.551 AC: 5819 AN: 10554

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42312 AN: 67952

Other (OTH) AF: 0.631 AC: 1334 AN: 2114

Alfa AF: 0.636 Hom.: 16288

Bravo AF: 0.624

Asia WGS AF: 0.785 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.81
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs4704843; hg19: chr5-156491153; COSMIC: COSV60219798;