rs2215413

Variant summary

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

The ENST00000577982.1(APOH):​c.-44+3027A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,760 control chromosomes in the GnomAD database, including 15,758 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 0.45 ( 15758 hom., cov: 31)

Consequence

APOH
ENST00000577982.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19
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]

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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=-1.03).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOHENST00000577982.1 linkc.-44+3027A>C intron_variant Intron 1 of 5 5 ENSP00000464301.1 J3QRN2

Frequencies

GnomAD3 genomes
AF:
0.447
AC:
67735
AN:
151642
Hom.:
15738
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.569
Gnomad AMI
AF:
0.476
Gnomad AMR
AF:
0.451
Gnomad ASJ
AF:
0.285
Gnomad EAS
AF:
0.179
Gnomad SAS
AF:
0.382
Gnomad FIN
AF:
0.361
Gnomad MID
AF:
0.278
Gnomad NFE
AF:
0.420
Gnomad OTH
AF:
0.385
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.447
AC:
67793
AN:
151760
Hom.:
15758
Cov.:
31
AF XY:
0.440
AC XY:
32633
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.569
Gnomad4 AMR
AF:
0.451
Gnomad4 ASJ
AF:
0.285
Gnomad4 EAS
AF:
0.179
Gnomad4 SAS
AF:
0.381
Gnomad4 FIN
AF:
0.361
Gnomad4 NFE
AF:
0.420
Gnomad4 OTH
AF:
0.382
Alfa
AF:
0.417
Hom.:
14627
Bravo
AF:
0.457
Asia WGS
AF:
0.321
AC:
1117
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.9
DANN
Benign
0.17

Splicing

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.

Other links and lift over

dbSNP: rs2215413; hg19: chr17-64249497; API