17-66230137-T-C

Variant names:

• chr17-66230137-T-C
• rs8178820
• ENST00000577982.1:c.-43-715A>G

Variant summary

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

The ENST00000577982.1(APOH):​c.-43-715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,608 control chromosomes in the GnomAD database, including 2,782 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 0.17 (2782 hom., cov: 31)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000577982.1	TSL:5	c.-43-715A>G		intron	N/A	ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25186 AN: 151492 Hom.: 2782 Cov.: 31

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.0645

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.166 AC: 25187 AN: 151608 Hom.: 2782 Cov.: 31 AF XY: 0.160 AC XY: 11824 AN XY: 74048

African (AFR) AF: 0.0515 AC: 2127 AN: 41324

American (AMR) AF: 0.118 AC: 1800 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.0648 AC: 333 AN: 5138

South Asian (SAS) AF: 0.0648 AC: 312 AN: 4812

European-Finnish (FIN) AF: 0.202 AC: 2107 AN: 10426

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17346 AN: 67920

Other (OTH) AF: 0.151 AC: 317 AN: 2106

Alfa AF: 0.224 Hom.: 5632

Bravo AF: 0.155

Asia WGS AF: 0.0650 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs8178820; hg19: chr17-64226255;