Genetic Variant HAVCR1:p.Leu179Pro (chr5-157052498-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001173393.3(HAVCR1):c.536T>C(p.Leu179Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,613,744 control chromosomes in the GnomAD database, including 594,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.87 ( 57328 hom., cov: 33)

Exomes 𝑓: 0.86 ( 536734 hom. )

Consequence

HAVCR1
NM_001173393.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.35

Publications

36 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1887994E-6).

BP6

Variant 5-157052498-A-G is Benign according to our data. Variant chr5-157052498-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059144.Status of the report is no_assertion_criteria_provided, 0 stars.

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 rank	MANE	Protein	UniProt
HAVCR1	NM_001173393.3 link	c.536T>C	p.Leu179Pro	missense_variant	Exon 4 of 9	ENST00000523175.6	NP_001166864.1	Q96D42B4DPB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAVCR1	ENST00000523175.6 link	c.536T>C	p.Leu179Pro	missense_variant	Exon 4 of 9	1	NM_001173393.3	ENSP00000427898.1		Q96D42

Frequencies

GnomAD3 genomes

AF:

0.868

AC:

131782

AN:

151798

Hom.:

57277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.982

Gnomad AMR

AF:

0.911

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.950

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.874

GnomAD2 exomes

AF:

0.884

AC:

220772

AN:

249610

AF XY:

0.886

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.936

Gnomad ASJ exome

AF:

0.902

Gnomad EAS exome

AF:

0.990

Gnomad FIN exome

AF:

0.846

Gnomad NFE exome

AF:

0.840

Gnomad OTH exome

AF:

0.869

GnomAD4 exome

AF:

0.856

AC:

1251008

AN:

1461828

Hom.:

536734

Cov.:

AF XY:

0.858

AC XY:

624291

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.878

AC:

29381

AN:

33480

American (AMR)

AF:

0.932

AC:

41677

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

23623

AN:

26136

East Asian (EAS)

AF:

0.982

AC:

38977

AN:

39700

South Asian (SAS)

AF:

0.954

AC:

82294

AN:

86258

European-Finnish (FIN)

AF:

0.846

AC:

45174

AN:

53418

Middle Eastern (MID)

AF:

0.877

AC:

5059

AN:

5768

European-Non Finnish (NFE)

AF:

0.839

AC:

932599

AN:

1111950

Other (OTH)

AF:

0.865

AC:

52224

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

11381

22763

34144

45526

56907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21142

42284

63426

84568

105710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.868

AC:

131890

AN:

151916

Hom.:

57328

Cov.:

AF XY:

0.872

AC XY:

64738

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.875

AC:

36261

AN:

41434

American (AMR)

AF:

0.911

AC:

13908

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

3143

AN:

3464

East Asian (EAS)

AF:

0.987

AC:

5091

AN:

5156

South Asian (SAS)

AF:

0.950

AC:

4574

AN:

4816

European-Finnish (FIN)

AF:

0.856

AC:

9046

AN:

10564

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

56876

AN:

67902

Other (OTH)

AF:

0.874

AC:

1842

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

923

1847

2770

3694

4617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.853

Hom.:

183121

Bravo

AF:

0.873

TwinsUK

AF:

0.845

AC:

3135

ALSPAC

AF:

0.840

AC:

3239

ESP6500AA

AF:

0.881

AC:

3746

ESP6500EA

AF:

0.840

AC:

7110

ExAC

AF:

0.884

AC:

107012

Asia WGS

AF:

0.957

AC:

3330

AN:

3478

EpiCase

AF:

0.847

EpiControl

AF:

0.845

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HAVCR1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.044

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.14

(source)

DANN

Benign

0.077

DEOGEN2

Benign

0.0069

T;.;.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00048

LIST_S2

Benign

0.25

.;.;T;T;T

MetaRNN

Benign

0.0000012

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-1.4

PrimateAI

Benign

0.20

PROVEAN

Benign

2.5

N;N;N;.;N

REVEL

Benign

0.017

Sift

Benign

0.25

T;T;T;.;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.0

B;.;.;B;.

Vest4

0.022

MPC

0.31

ClinPred

0.0022

GERP RS

-2.3

gMVP

0.080

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over