rs6555810

chr5-157030975-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.987-1134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 151,440 control chromosomes in the GnomAD database, including 466 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 0.049 (466 hom., cov: 32)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.987-1134A>G		intron_variant		ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.987-1134A>G		intron_variant		1	NM_001173393.3	P2
HAVCR1	ENST00000339252.8	c.987-1134A>G		intron_variant		1		P2
HAVCR1	ENST00000522693.5	c.953-1134A>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7426 AN: 151340 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00404

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0381

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

GnomAD4 genome AF: 0.0492 AC: 7455 AN: 151440 Hom.: 466 Cov.: 32 AF XY: 0.0466 AC XY: 3444 AN XY: 73964

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.00188

Gnomad4 FIN AF: 0.00404

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0400

Alfa AF: 0.0374 Hom.: 51

Bravo AF: 0.0551

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.47

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: rs6555810; hg19: chr5-156457986;