Variant 5-157052477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.14

Variant links:

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]

HAVCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	Protein	UniProt
HAVCR1	NM_001173393.3 linkuse as main transcript	c.557C>T	p.Thr186Met	missense_variant	4/9	ENST00000523175.6	NP_001166864.1	Q96D42B4DPB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6 linkuse as main transcript	c.557C>T	p.Thr186Met	missense_variant	4/9	1	NM_001173393.3	ENSP00000427898.1		Q96D42

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3082

AN:

152162

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00385

AC XY:

521

AN XY:

135410

show subpopulations

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.:

AF XY:

0.00182

AC XY:

1310

AN XY:

721630

show subpopulations

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.:

Cov.:

AF XY:

0.0195

AC XY:

1454

AN XY:

74462

show subpopulations

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.:

Bravo

AF:

0.0232

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0611

AC:

259

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00599

AC:

725

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HAVCR1-related disorder

Benign:1

Benign, no assertion criteria provided

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.79

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

LIST_S2

Benign

0.40

.;.;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.18

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over