Variant 17-66229411-G-T 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.-32C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,602,734 control chromosomes in the GnomAD database, including 3,551 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.

Frequency

Genomes: 𝑓 0.067 ( 326 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3225 hom. )

Consequence

APOH
NM_000042.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOH	NM_000042.3 linkuse as main transcript	c.-32C>A		5_prime_UTR_variant	1/8	ENST00000205948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000205948.11 linkuse as main transcript	c.-32C>A		5_prime_UTR_variant	1/8	1	NM_000042.3	P1
APOH	ENST00000577982.1 linkuse as main transcript	c.-32C>A		5_prime_UTR_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.0666

AC:

10127

AN:

152100

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0744

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0715

Gnomad EAS

AF:

0.0645

Gnomad SAS

AF:

0.0535

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0664

GnomAD3 exomes

AF:

0.0626

AC:

15405

AN:

246174

Hom.:

563

AF XY:

0.0625

AC XY:

8317

AN XY:

133104

show subpopulations

Gnomad AFR exome

AF:

0.0746

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0661

Gnomad EAS exome

AF:

0.0616

Gnomad SAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.0970

Gnomad NFE exome

AF:

0.0671

Gnomad OTH exome

AF:

0.0672

GnomAD4 exome

AF:

0.0652

AC:

94573

AN:

1450516

Hom.:

3225

Cov.:

AF XY:

0.0653

AC XY:

47107

AN XY:

721778

show subpopulations

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0696

Gnomad4 EAS exome

AF:

0.0717

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.0949

Gnomad4 NFE exome

AF:

0.0661

Gnomad4 OTH exome

AF:

0.0597

GnomAD4 genome

AF:

0.0666

AC:

10138

AN:

152218

Hom.:

326

Cov.:

AF XY:

0.0666

AC XY:

4957

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0745

Gnomad4 AMR

AF:

0.0454

Gnomad4 ASJ

AF:

0.0715

Gnomad4 EAS

AF:

0.0643

Gnomad4 SAS

AF:

0.0535

Gnomad4 FIN

AF:

0.0896

Gnomad4 NFE

AF:

0.0642

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0620

Hom.:

311

Bravo

AF:

0.0628

Asia WGS

AF:

0.0580

AC:

200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

DANN

Benign

0.57

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