rs8178819

Variant names:

• chr17-66230597-C-T
• rs8178819
• ENST00000577982.1:c.-43-1175G>A

Variant summary

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

The ENST00000577982.1(APOH):​c.-43-1175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 152,284 control chromosomes in the GnomAD database, including 291 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 0.052 (291 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000577982.1	TSL:5	c.-43-1175G>A		intron	N/A	ENSP00000464301.1	J3QRN2

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7914 AN: 152166 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0565

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

GnomAD4 genome AF: 0.0520 AC: 7915 AN: 152284 Hom.: 291 Cov.: 32 AF XY: 0.0507 AC XY: 3776 AN XY: 74476

African (AFR) AF: 0.0143 AC: 593 AN: 41564

American (AMR) AF: 0.0473 AC: 723 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4830

European-Finnish (FIN) AF: 0.0658 AC: 698 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0793 AC: 5396 AN: 68024

Other (OTH) AF: 0.0559 AC: 118 AN: 2110

Alfa AF: 0.0648 Hom.: 343

Bravo AF: 0.0492

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.46
PhyloP100		-0.37

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs8178819;

hg19: chr17-64226715;