5-157052413-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001173393.3(HAVCR1):c.621T>G(p.Thr207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,613,720 control chromosomes in the GnomAD database, including 594,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57539 hom., cov: 34)
  • Exomes 𝑓: 0.86 (536718 hom.)
• Consequence: HAVCR1 NM_001173393.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 5-157052413-A-C is Benign according to our data. Variant chr5-157052413-A-C is described in ClinVar as [Benign]. Clinvar id is 3059346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.621T>G	p.Thr207=	synonymous_variant	4/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.621T>G	p.Thr207=	synonymous_variant	4/9	1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132164 AN: 152138 Hom.: 57488 Cov.: 34

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.876

GnomAD3 exomes AF: 0.884 AC: 220762 AN: 249590 Hom.: 98030 AF XY: 0.886 AC XY: 119983 AN XY: 135406

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.902

Gnomad EAS exome AF: 0.989

Gnomad SAS exome AF: 0.956

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.840

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.856 AC: 1250808 AN: 1461464 Hom.: 536718 Cov.: 48 AF XY: 0.859 AC XY: 624204 AN XY: 727046

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.932

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.869 AC: 132272 AN: 152256 Hom.: 57539 Cov.: 34 AF XY: 0.872 AC XY: 64945 AN XY: 74436

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.950

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.875

Alfa AF: 0.850 Hom.: 66007

Bravo AF: 0.873

EpiCase AF: 0.847

EpiControl AF: 0.845

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HAVCR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.28
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1553317; hg19: chr5-156479424;