rs12522248

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T207I) has been classified as Uncertain significance.

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

Publications

35 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=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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HAVCR1	NM_001173393.3	MANE Select	c.619A>G	p.Thr207Ala	missense	Exon 4 of 9	NP_001166864.1
HAVCR1	NM_001308156.2		c.619A>G	p.Thr207Ala	missense	Exon 4 of 8	NP_001295085.1
HAVCR1	NM_012206.3		c.619A>G	p.Thr207Ala	missense	Exon 3 of 8	NP_036338.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HAVCR1	ENST00000523175.6	TSL:1 MANE Select	c.619A>G	p.Thr207Ala	missense	Exon 4 of 9	ENSP00000427898.1
HAVCR1	ENST00000339252.8	TSL:1	c.619A>G	p.Thr207Ala	missense	Exon 3 of 8	ENSP00000344844.3
HAVCR1	ENST00000522693.5	TSL:2	c.619A>G	p.Thr207Ala	missense	Exon 4 of 8	ENSP00000428524.1

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

GnomAD2 exomes

AF:

0.288

AC:

71875

AN:

249582

AF XY:

0.285

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 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

African (AFR)

AF:

0.164

AC:

5483

AN:

33468

American (AMR)

AF:

0.420

AC:

18767

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

7968

AN:

26132

East Asian (EAS)

AF:

0.137

AC:

5453

AN:

39694

South Asian (SAS)

AF:

0.266

AC:

22978

AN:

86244

European-Finnish (FIN)

AF:

0.270

AC:

14438

AN:

53420

Middle Eastern (MID)

AF:

0.309

AC:

1783

AN:

5764

European-Non Finnish (NFE)

AF:

0.290

AC:

321819

AN:

1111316

Other (OTH)

AF:

0.272

AC:

16397

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16854

33708

50562

67416

84270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10750

21500

32250

43000

53750

<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:

0.262

AC:

39124

AN:

149248

Hom.:

5425

Cov.:

AF XY:

0.263

AC XY:

19145

AN XY:

72866

show subpopulations

African (AFR)

AF:

0.175

AC:

6965

AN:

39786

American (AMR)

AF:

0.358

AC:

5370

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1095

AN:

3436

East Asian (EAS)

AF:

0.156

AC:

802

AN:

5140

South Asian (SAS)

AF:

0.273

AC:

1287

AN:

4710

European-Finnish (FIN)

AF:

0.286

AC:

2995

AN:

10466

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19614

AN:

67442

Other (OTH)

AF:

0.296

AC:

614

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1521

3043

4564

6086

7607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.279

Hom.:

24592

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.28

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0064

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.93

PhyloP100

-0.71

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.27

REVEL

Benign

0.12

Sift

Benign

0.55

Sift4G

Benign

0.46

Polyphen

0.015

Vest4

0.025

MPC

0.19

ClinPred

0.011

GERP RS

1.1

gMVP

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over