Variant 5-157052453-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001173393.3(HAVCR1):c.581C>T(p.Thr194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,603,852 control chromosomes in the GnomAD database, including 87 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 0.013 ( 47 hom., cov: 35)

Exomes 𝑓: 0.0013 ( 40 hom. )

Consequence

HAVCR1
NM_001173393.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.598

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=0.002854973).

BP6

Variant 5-157052453-G-A is Benign according to our data. Variant chr5-157052453-G-A is described in ClinVar as [Benign]. Clinvar id is 769669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1981/152302) while in subpopulation AFR AF= 0.0442 (1836/41556). AF 95% confidence interval is 0.0425. There are 47 homozygotes in gnomad4. There are 948 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAVCR1	NM_001173393.3 linkuse as main transcript	c.581C>T	p.Thr194Met	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.581C>T	p.Thr194Met	missense_variant	4/9	1	NM_001173393.3	ENSP00000427898.1		Q96D42

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1958

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00321

AC:

802

AN:

249600

Hom.:

AF XY:

0.00246

AC XY:

333

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.00133

AC:

1929

AN:

1451550

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

795

AN XY:

721790

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000805

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.0130

AC:

1981

AN:

152302

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0442

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.0153

ESP6500AA

AF:

0.0422

AC:

177

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.00391

AC:

473

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.82

DEOGEN2

Benign

0.024

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.43

.;.;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.93

N;N;N;.;N

REVEL

Benign

0.028

Sift

Benign

0.58

T;T;T;.;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.0050

B;.;.;B;.

Vest4

0.17

MVP

0.061

MPC

0.20

ClinPred

0.00099

GERP RS

-0.54

gMVP

0.23

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