5-157033084-T-C

Variant summary

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

The NM_001173393.3(HAVCR1):c.953-197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,042 control chromosomes in the GnomAD database, including 8,762 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 (8762 hom., cov: 31)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.953-197A>G		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.953-197A>G		intron_variant		1	NM_001173393.3	P2
HAVCR1	ENST00000339252.8	c.953-197A>G		intron_variant		1		P2
HAVCR1	ENST00000522693.5	c.953-3243A>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47249 AN: 151924 Hom.: 8749 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.311 AC: 47272 AN: 152042 Hom.: 8762 Cov.: 31 AF XY: 0.319 AC XY: 23722 AN XY: 74296

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.310

Alfa AF: 0.362 Hom.: 20717

Bravo AF: 0.295

Asia WGS AF: 0.522 AC: 1813 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	1.6
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277025; hg19: chr5-156460095;