Variant rs1801690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000042.3(APOH):c.1004G>C(p.Trp335Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0514 in 1,612,074 control chromosomes in the GnomAD database, including 2,408 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.040 ( 168 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2240 hom. )

Consequence

APOH
NM_000042.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.84

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011089236).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOH	NM_000042.3 linkuse as main transcript	c.1004G>C	p.Trp335Ser	missense_variant	8/8	ENST00000205948.11	NP_000033.2	P02749A0A384NKM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11 linkuse as main transcript	c.1004G>C	p.Trp335Ser	missense_variant	8/8	1	NM_000042.3	ENSP00000205948.6		P02749
APOH	ENST00000585162.1 linkuse as main transcript	c.278G>C	p.Trp93Ser	missense_variant	3/3	2		ENSP00000462260.1		J3KS17

Frequencies

GnomAD3 genomes

AF:

0.0405

AC:

6161

AN:

151982

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00868

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.0387

Gnomad EAS

AF:

0.0707

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.0705

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0545

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0479

AC:

12020

AN:

251190

Hom.:

377

AF XY:

0.0492

AC XY:

6680

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.0667

Gnomad SAS exome

AF:

0.0472

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.0555

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0525

AC:

76641

AN:

1459974

Hom.:

2240

Cov.:

AF XY:

0.0528

AC XY:

38334

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.00601

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0322

Gnomad4 EAS exome

AF:

0.0872

Gnomad4 SAS exome

AF:

0.0462

Gnomad4 FIN exome

AF:

0.0733

Gnomad4 NFE exome

AF:

0.0545

Gnomad4 OTH exome

AF:

0.0434

GnomAD4 genome

AF:

0.0405

AC:

6160

AN:

152100

Hom.:

168

Cov.:

AF XY:

0.0409

AC XY:

3039

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00865

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.0387

Gnomad4 EAS

AF:

0.0703

Gnomad4 SAS

AF:

0.0511

Gnomad4 FIN

AF:

0.0705

Gnomad4 NFE

AF:

0.0546

Gnomad4 OTH

AF:

0.0364

Alfa

AF:

0.0518

Hom.:

165

Bravo

AF:

0.0351

TwinsUK

AF:

0.0547

AC:

203

ALSPAC

AF:

0.0571

AC:

220

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0513

AC:

441

ExAC

AF:

0.0487

AC:

5909

Asia WGS

AF:

0.0520

AC:

179

AN:

3478

EpiCase

AF:

0.0530

EpiControl

AF:

0.0549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.73

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.17

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.23

MPC

0.46

ClinPred

0.016

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.76

gMVP

0.73

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over