17-66214410-G-A

Position:

• chr17-66214410-G-A

Variant summary

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

The ENST00000205948.11(APOH):​c.982+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,542,258 control chromosomes in the GnomAD database, including 40,866 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 (2790 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38076 hom.)
• Consequence: APOH ENST00000205948.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOH	NM_000042.3	c.982+43C>T		intron_variant		ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.982+43C>T		intron_variant		1	NM_000042.3	ENSP00000205948	P1
APOH	ENST00000585162.1	c.258-2222C>T		intron_variant		2		ENSP00000462260

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25232 AN: 151830 Hom.: 2790 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.167 AC: 41269 AN: 247214 Hom.: 4407 AF XY: 0.167 AC XY: 22355 AN XY: 133778

Gnomad AFR exome AF: 0.0450

Gnomad AMR exome AF: 0.0856

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0559

Gnomad SAS exome AF: 0.0634

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.222 AC: 308884 AN: 1390310 Hom.: 38076 Cov.: 22 AF XY: 0.218 AC XY: 151515 AN XY: 696048

Gnomad4 AFR exome AF: 0.0415

Gnomad4 AMR exome AF: 0.0891

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0676

Gnomad4 SAS exome AF: 0.0681

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.166 AC: 25234 AN: 151948 Hom.: 2790 Cov.: 32 AF XY: 0.160 AC XY: 11846 AN XY: 74262

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0657

Gnomad4 SAS AF: 0.0645

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.151

Alfa AF: 0.229 Hom.: 4264

Bravo AF: 0.155

Asia WGS AF: 0.0650 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1544556; hg19: chr17-64210528;