5-157039168-G-T

Variant names:

• chr5-157039168-G-T
• rs1501909
• NM_001173393.3:c.838-1807C>A

Variant summary

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

The NM_001173393.3(HAVCR1):​c.838-1807C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,966 control chromosomes in the GnomAD database, including 8,646 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 0.31 (8646 hom., cov: 32)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 8 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.838-1807C>A		intron_variant	Intron 6 of 8	ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6	c.838-1807C>A		intron_variant	Intron 6 of 8	1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46665 AN: 151848 Hom.: 8635 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.307 AC: 46688 AN: 151966 Hom.: 8646 Cov.: 32 AF XY: 0.317 AC XY: 23554 AN XY: 74260

African (AFR) AF: 0.103 AC: 4277 AN: 41464

American (AMR) AF: 0.340 AC: 5195 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3391 AN: 5170

South Asian (SAS) AF: 0.503 AC: 2424 AN: 4820

European-Finnish (FIN) AF: 0.425 AC: 4475 AN: 10532

Middle Eastern (MID) AF: 0.203 AC: 59 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24535 AN: 67938

Other (OTH) AF: 0.304 AC: 643 AN: 2112

Alfa AF: 0.325 Hom.: 1359

Bravo AF: 0.289

Asia WGS AF: 0.530 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.88
PhyloP100		0.26
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: rs1501909; hg19: chr5-156466179;