17-66214639-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000042.3(APOH):c.796G>T(p.Val266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,608,964 control chromosomes in the GnomAD database, including 85,022 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 11892 hom., cov: 32)

Exomes 𝑓: 0.29 ( 73130 hom. )

Consequence

APOH
NM_000042.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.214

Publications

53 publications found

Variant links:

Genes affected

APOH (HGNC:616): (apolipoprotein H) Apolipoprotein H, also known as beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It has been implicated in a variety of physiologic pathways including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a required cofactor for anionic phospholipid binding by the antiphospholipid autoantibodies found in sera of many patients with lupus and primary antiphospholipid syndrome (APS). The anti-beta (2) glycoprotein I antibodies from APS patients, mediate inhibition of activated protein C which has anticoagulant properties. Because beta-2-GPI is the main autoantigen in patients with APS, the disruption of this pathway by autoantibodies may be an important mechanism for thrombosis in patients with APS.[provided by RefSeq, Dec 2019]

APOH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.019869E-7).

BP6

Variant 17-66214639-C-A is Benign according to our data. Variant chr17-66214639-C-A is described in ClinVar as [Benign]. Clinvar id is 16042.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3 link	c.796G>T	p.Val266Leu	missense_variant	Exon 7 of 8	ENST00000205948.11	NP_000033.2	P02749A0A384NKM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11 link	c.796G>T	p.Val266Leu	missense_variant	Exon 7 of 8	1	NM_000042.3	ENSP00000205948.6		P02749
APOH	ENST00000585162.1 link	c.256+2149G>T		intron_variant	Intron 2 of 2	2		ENSP00000462260.1		J3KS17

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55155

AN:

151794

Hom.:

11867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.340

GnomAD2 exomes

AF:

0.376

AC:

93812

AN:

249772

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.769

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.287

AC:

418354

AN:

1457052

Hom.:

73130

Cov.:

AF XY:

0.293

AC XY:

212258

AN XY:

725110

show subpopulations

African (AFR)

AF:

0.530

AC:

17571

AN:

33132

American (AMR)

AF:

0.546

AC:

24049

AN:

44024

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

6455

AN:

26084

East Asian (EAS)

AF:

0.772

AC:

30594

AN:

39628

South Asian (SAS)

AF:

0.551

AC:

47363

AN:

85948

European-Finnish (FIN)

AF:

0.254

AC:

13554

AN:

53364

Middle Eastern (MID)

AF:

0.264

AC:

1519

AN:

5756

European-Non Finnish (NFE)

AF:

0.233

AC:

258049

AN:

1108940

Other (OTH)

AF:

0.319

AC:

19200

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

12273

24545

36818

49090

61363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.364

AC:

55229

AN:

151912

Hom.:

11892

Cov.:

AF XY:

0.373

AC XY:

27665

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.512

AC:

21198

AN:

41424

American (AMR)

AF:

0.456

AC:

6953

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3466

East Asian (EAS)

AF:

0.759

AC:

3910

AN:

5152

South Asian (SAS)

AF:

0.565

AC:

2720

AN:

4816

European-Finnish (FIN)

AF:

0.245

AC:

2582

AN:

10540

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15919

AN:

67938

Other (OTH)

AF:

0.348

AC:

734

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1618

3236

4855

6473

8091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.283

Hom.:

22158

Bravo

AF:

0.385

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.237

AC:

913

ESP6500AA

AF:

0.510

AC:

2245

ESP6500EA

AF:

0.238

AC:

2043

ExAC

AF:

0.374

AC:

45380

Asia WGS

AF:

0.629

AC:

2183

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

APOH POLYMORPHISM

Benign:1

May 01, 1993

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.090

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.65

MetaRNN

Benign

9.0e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.58

PhyloP100

-0.21

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.50

REVEL

Benign

0.022

Sift

Benign

0.67

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.053

MutPred

0.23

Loss of catalytic residue at V266 (P = 0.069);

MPC

0.15

ClinPred

0.0020

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.074

gMVP

0.40

Mutation Taster

=94/6

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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17-66214639-C-A

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