Variant rs12522248 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001173393.3(HAVCR1):c.619A>G(p.Thr207Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,610,364 control chromosomes in the GnomAD database, including 66,117 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. T207T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.26 ( 5425 hom., cov: 35)

Exomes 𝑓: 0.28 ( 60692 hom. )

Consequence

HAVCR1
NM_001173393.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.709

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026894212).

BP6

Variant 5-157052415-T-C is Benign according to our data. Variant chr5-157052415-T-C is described in ClinVar as [Benign]. Clinvar id is 3060126.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAVCR1	NM_001173393.3 linkuse as main transcript	c.619A>G	p.Thr207Ala	missense_variant	4/9	ENST00000523175.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAVCR1	ENST00000523175.6 linkuse as main transcript	c.619A>G	p.Thr207Ala	missense_variant	4/9	1	NM_001173393.3	P2

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39111

AN:

149146

Hom.:

5421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.288

AC:

71875

AN:

249582

Hom.:

11232

AF XY:

0.285

AC XY:

38624

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.284

AC:

415086

AN:

1461116

Hom.:

60692

Cov.:

AF XY:

0.284

AC XY:

206123

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.420

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.262

AC:

39124

AN:

149248

Hom.:

5425

Cov.:

AF XY:

0.263

AC XY:

19145

AN XY:

72866

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.285

Hom.:

13393

Bravo

AF:

0.261

TwinsUK

AF:

0.291

AC:

1078

ALSPAC

AF:

0.291

AC:

1120

ESP6500AA

AF:

0.170

AC:

698

ESP6500EA

AF:

0.285

AC:

2393

ExAC

AF:

0.279

AC:

33713

EpiCase

AF:

0.303

EpiControl

AF:

0.301

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HAVCR1-related disorder

Benign:1

Benign, no assertion criteria provided

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.28

DANN

Benign

0.18

DEOGEN2

Benign

0.0064

T;.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.14

.;.;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.27

N;N;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.55

T;T;T;.;T

Sift4G

Benign

0.46

T;T;T;T;T

Polyphen

0.015

B;.;.;B;.

Vest4

0.025

MPC

0.19

ClinPred

0.011

GERP RS

1.1

gMVP

0.11

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