5-157052477-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001173393.3(HAVCR1):c.557C>T(p.Thr186Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,603,226 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (91 hom., cov: 35)
  • Exomes 𝑓: 0.0021 (110 hom.)
• Consequence: HAVCR1 NM_001173393.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.14

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023442209).
• BP6: Variant 5-157052477-G-A is Benign according to our data. Variant chr5-157052477-G-A is described in ClinVar as [Benign]. Clinvar id is 783620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3	c.557C>T	p.Thr186Met	missense_variant	4/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6	c.557C>T	p.Thr186Met	missense_variant	4/9	1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3082 AN: 152162 Hom.: 90 Cov.: 35

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00502 AC: 1252 AN: 249614 Hom.: 38 AF XY: 0.00385 AC XY: 521 AN XY: 135410

Gnomad AFR exome AF: 0.0698

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00208 AC: 3013 AN: 1450946 Hom.: 110 Cov.: 53 AF XY: 0.00182 AC XY: 1310 AN XY: 721630

Gnomad4 AFR exome AF: 0.0726

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.000259

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.00504

GnomAD4 genome AF: 0.0203 AC: 3092 AN: 152280 Hom.: 91 Cov.: 35 AF XY: 0.0195 AC XY: 1454 AN XY: 74462

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.00419 Hom.: 38

Bravo AF: 0.0232

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0611 AC: 259

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00599 AC: 725

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

HAVCR1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.063
Dann	Benign	0.56
DEOGEN2	Benign	0.022	T;.;.;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.0023	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.59	N;N;N;.;N
REVEL	Benign	0.0020
Sift	Benign	0.47	T;T;T;.;T
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.0010	B;.;.;B;.
Vest4		0.11
MVP		0.061
MPC		0.20
ClinPred		0.00020	T
GERP RS		-3.7
gMVP		0.21

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: rs73815912; hg19: chr5-156479488; COSMIC: COSV59398329; COSMIC: COSV59398329;