Variant chr17-66214462-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000205948.11(APOH):c.973T>G(p.Cys325Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0281 in 1,613,586 control chromosomes in the GnomAD database, including 770 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 0.023 ( 57 hom., cov: 32)

Exomes 𝑓: 0.029 ( 713 hom. )

Consequence

APOH
ENST00000205948.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.76

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=0.010155737).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0686 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.973T>G	p.Cys325Gly	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 linkuse as main transcript	c.973T>G	p.Cys325Gly	missense_variant	7/8	1	NM_000042.3	ENSP00000205948.6		P02749
APOH	ENST00000585162.1 linkuse as main transcript	c.257-2274T>G		intron_variant		2		ENSP00000462260.1		J3KS17

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3503

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.00528

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0334

Gnomad OTH

AF:

0.0353

GnomAD3 exomes

AF:

0.0245

AC:

6137

AN:

250782

Hom.:

120

AF XY:

0.0249

AC XY:

3369

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00585

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.00818

Gnomad NFE exome

AF:

0.0328

Gnomad OTH exome

AF:

0.0344

GnomAD4 exome

AF:

0.0286

AC:

41833

AN:

1461280

Hom.:

713

Cov.:

AF XY:

0.0287

AC XY:

20879

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.00598

Gnomad4 AMR exome

AF:

0.0273

Gnomad4 ASJ exome

AF:

0.0590

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.00872

Gnomad4 NFE exome

AF:

0.0312

Gnomad4 OTH exome

AF:

0.0314

GnomAD4 genome

AF:

0.0230

AC:

3499

AN:

152306

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1636

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00628

Gnomad4 AMR

AF:

0.0341

Gnomad4 ASJ

AF:

0.0628

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.00528

Gnomad4 NFE

AF:

0.0334

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0300

Hom.:

146

Bravo

AF:

0.0239

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0275

AC:

106

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.0364

AC:

313

ExAC

AF:

0.0240

AC:

2919

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.8

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

MPC

0.75

ClinPred

0.042

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.96

gMVP

0.97

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