Variant 17-66220736-A-G 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.422T>C(p.Ile141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,602,108 control chromosomes in the GnomAD database, including 3,692 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.073 ( 426 hom., cov: 31)

Exomes 𝑓: 0.065 ( 3266 hom. )

Consequence

APOH
NM_000042.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.32

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031048357).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 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.422T>C	p.Ile141Thr	missense_variant	5/8	ENST00000205948.11	NP_000033.2	P02749A0A384NKM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOH	ENST00000205948.11 linkuse as main transcript	c.422T>C	p.Ile141Thr	missense_variant	5/8	1	NM_000042.3	ENSP00000205948.6	P02749
APOH	ENST00000581797.5 linkuse as main transcript	c.242T>C	p.Ile81Thr	missense_variant	5/6	3		ENSP00000463553.1	J3QLI0
APOH	ENST00000577982.1 linkuse as main transcript	c.422T>C	p.Ile141Thr	missense_variant	6/6	5		ENSP00000464301.1	J3QRN2

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

11109

AN:

152090

Hom.:

423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0978

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0466

Gnomad ASJ

AF:

0.0714

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0890

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0641

Gnomad OTH

AF:

0.0703

GnomAD3 exomes

AF:

0.0644

AC:

16061

AN:

249456

Hom.:

610

AF XY:

0.0639

AC XY:

8606

AN XY:

134748

show subpopulations

Gnomad AFR exome

AF:

0.0986

Gnomad AMR exome

AF:

0.0300

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.0616

Gnomad SAS exome

AF:

0.0515

Gnomad FIN exome

AF:

0.0971

Gnomad NFE exome

AF:

0.0671

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0649

AC:

94052

AN:

1449900

Hom.:

3266

Cov.:

AF XY:

0.0650

AC XY:

46767

AN XY:

719726

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0697

Gnomad4 EAS exome

AF:

0.0714

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.0948

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0611

GnomAD4 genome

AF:

0.0731

AC:

11123

AN:

152208

Hom.:

426

Cov.:

AF XY:

0.0724

AC XY:

5390

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0979

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0714

Gnomad4 EAS

AF:

0.0639

Gnomad4 SAS

AF:

0.0533

Gnomad4 FIN

AF:

0.0890

Gnomad4 NFE

AF:

0.0642

Gnomad4 OTH

AF:

0.0701

Alfa

AF:

0.0658

Hom.:

445

Bravo

AF:

0.0702

TwinsUK

AF:

0.0642

AC:

238

ALSPAC

AF:

0.0693

AC:

267

ESP6500AA

AF:

0.0901

AC:

397

ESP6500EA

AF:

0.0651

AC:

560

ExAC

AF:

0.0658

AC:

7984

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.0643

EpiControl

AF:

0.0686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.091

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.18

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.9

N;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

2.7

N;.;.

REVEL

Benign

0.065

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;.;.

Polyphen

0.0

B;.;.

Vest4

0.053

MPC

0.20

ClinPred

0.0043

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.42

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