chr5-157052312-G-C

Position:

• chr5-157052312-G-C

Variant summary

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

The NM_001173393.3(HAVCR1):​c.673+49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,542,454 control chromosomes in the GnomAD database, including 320,365 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 0.60 (27959 hom., cov: 32)
  • Exomes 𝑓: 0.64 (292406 hom.)
• Consequence: HAVCR1 NM_001173393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR1	NM_001173393.3	c.673+49C>G		intron_variant		ENST00000523175.6	NP_001166864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6	c.673+49C>G		intron_variant		1	NM_001173393.3	ENSP00000427898.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90552 AN: 151950 Hom.: 27935 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.611

GnomAD3 exomes AF: 0.670 AC: 162163 AN: 241998 Hom.: 55681 AF XY: 0.671 AC XY: 87979 AN XY: 131210

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.802

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.807

Gnomad SAS exome AF: 0.739

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.629

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.645 AC: 896183 AN: 1390386 Hom.: 292406 Cov.: 22 AF XY: 0.647 AC XY: 449502 AN XY: 694766

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.790

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152068 Hom.: 27959 Cov.: 32 AF XY: 0.605 AC XY: 44937 AN XY: 74330

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.611

Alfa AF: 0.549 Hom.: 3103

Bravo AF: 0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.34

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: rs1553318; hg19: chr5-156479323;