Variant rs4581 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APOH	NM_000042.3 link	c.796G>T	p.Val266Leu	missense_variant	7/8	ENST00000205948.11	NP_000033.2	P02749A0A384NKM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11 link	c.796G>T	p.Val266Leu	missense_variant	7/8	1	NM_000042.3	ENSP00000205948.6		P02749
APOH	ENST00000585162.1 link	c.256+2149G>T		intron_variant		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

GnomAD3 exomes

AF:

0.376

AC:

93812

AN:

249772

Hom.:

21980

AF XY:

0.370

AC XY:

49981

AN XY:

135096

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 SAS exome

AF:

0.549

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

Gnomad4 AFR exome

AF:

0.530

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.772

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.364

AC:

55229

AN:

151912

Hom.:

11892

Cov.:

AF XY:

0.373

AC XY:

27665

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.512

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.565

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.265

Hom.:

12015

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

Benign, no assertion criteria provided

literature only

OMIM

May 01, 1993

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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

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

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