17-66230568-C-G

Position:

• chr17-66230568-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000577982.1(APOH):​c.-43-1146G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,072 control chromosomes in the GnomAD database, including 8,645 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 0.33 (8645 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.66230568C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000577982.1	c.-43-1146G>C		intron_variant		5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50373 AN: 151954 Hom.: 8634 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.332 AC: 50423 AN: 152072 Hom.: 8645 Cov.: 32 AF XY: 0.323 AC XY: 23978 AN XY: 74330

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.296

Alfa AF: 0.244 Hom.: 682

Bravo AF: 0.326

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3760290; hg19: chr17-64226686;