17-66230568-C-G

Variant names:

• chr17-66230568-C-G
• rs3760290
• ENST00000577982.1:c.-43-1146G>C

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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000577982.1	c.-43-1146G>C		intron_variant	Intron 1 of 5	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;