NM_001173393.3:c.674-1244A>C

Variant names:

• chr5-157050389-T-G
• rs953569
• NM_001173393.3:c.674-1244A>C

Variant summary

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

The NM_001173393.3(HAVCR1):​c.674-1244A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,926 control chromosomes in the GnomAD database, including 17,461 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 0.48 (17461 hom., cov: 32)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.674-1244A>C		intron_variant	Intron 4 of 8	ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6	c.674-1244A>C		intron_variant	Intron 4 of 8	1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72547 AN: 151808 Hom.: 17457 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.478 AC: 72584 AN: 151926 Hom.: 17461 Cov.: 32 AF XY: 0.475 AC XY: 35265 AN XY: 74276

African (AFR) AF: 0.506 AC: 20935 AN: 41410

American (AMR) AF: 0.530 AC: 8093 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1688 AN: 5162

South Asian (SAS) AF: 0.449 AC: 2160 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4532 AN: 10552

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31635 AN: 67944

Other (OTH) AF: 0.505 AC: 1066 AN: 2112

Alfa AF: 0.439 Hom.: 4724

Bravo AF: 0.488

Asia WGS AF: 0.410 AC: 1430 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	1.1
DANN	Benign	0.38
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs953569; hg19: chr5-156477400;