17-66246585-G-C

Variant names:

• chr17-66246585-G-C
• rs8064837
• ENST00000577982.1:c.-44+9821C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000577982.1(APOH):​c.-44+9821C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,014 control chromosomes in the GnomAD database, including 30,477 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 0.62 (30477 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577982.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000577982.1	TSL:5	c.-44+9821C>G		intron	N/A	ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94145 AN: 151896 Hom.: 30423 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.620 AC: 94266 AN: 152014 Hom.: 30477 Cov.: 32 AF XY: 0.621 AC XY: 46165 AN XY: 74298

African (AFR) AF: 0.777 AC: 32243 AN: 41494

American (AMR) AF: 0.619 AC: 9439 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4438 AN: 5172

South Asian (SAS) AF: 0.639 AC: 3073 AN: 4812

European-Finnish (FIN) AF: 0.520 AC: 5471 AN: 10528

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36065 AN: 67976

Other (OTH) AF: 0.577 AC: 1215 AN: 2104

Alfa AF: 0.579 Hom.: 3081

Bravo AF: 0.634

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8064837; hg19: chr17-64242703;