17-66220679-G-T

Position:

chr17-66220679-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000042.3(APOH):c.479C>A(p.Ala160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,614,138 control chromosomes in the GnomAD database, including 18 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 0.0058 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 11 hom. )

Consequence

APOH
NM_000042.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.983

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051770806).

BP6

Variant 17-66220679-G-T is Benign according to our data. Variant chr17-66220679-G-T is described in ClinVar as [Benign]. Clinvar id is 780447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (883/152282) while in subpopulation AFR AF= 0.0205 (850/41560). AF 95% confidence interval is 0.0193. There are 7 homozygotes in gnomad4. There are 406 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOH	NM_000042.3 linkuse as main transcript	c.479C>A	p.Ala160Asp	missense_variant	5/8	ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
APOH	ENST00000205948.11 linkuse as main transcript	c.479C>A	p.Ala160Asp	missense_variant	5/8	1	NM_000042.3	ENSP00000205948	P1
APOH	ENST00000581797.5 linkuse as main transcript	c.299C>A	p.Ala100Asp	missense_variant	5/6	3		ENSP00000463553
APOH	ENST00000577982.1 linkuse as main transcript	c.479C>A	p.Ala160Asp	missense_variant	6/6	5		ENSP00000464301
APOH	ENST00000585162.1 linkuse as main transcript			upstream_gene_variant		2		ENSP00000462260

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

883

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00153

AC:

384

AN:

251402

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000558

AC:

815

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

315

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0205

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00580

AC:

883

AN:

152282

Hom.:

Cov.:

AF XY:

0.00545

AC XY:

406

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000976

Hom.:

Bravo

AF:

0.00631

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00187

AC:

227

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.12

T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.96

N;.;.

REVEL

Benign

0.044

Sift

Benign

0.39

T;.;.

Sift4G

Benign

0.24

T;.;.

Polyphen

0.24

B;.;.

Vest4

0.23

MVP

0.17

MPC

0.33

ClinPred

0.0025

GERP RS

0.92

Varity_R

0.21

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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