rs6933

Positions:

• chr17-66212112-G-A

Variant summary

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

The NM_000042.3(APOH):​c.*21C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,595,720 control chromosomes in the GnomAD database, including 283,535 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 0.65 (33707 hom., cov: 33)
  • Exomes 𝑓: 0.58 (249828 hom.)
• Consequence: APOH NM_000042.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOH	NM_000042.3	c.*21C>T		3_prime_UTR_variant	8/8	ENST00000205948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000205948.11	c.*21C>T		3_prime_UTR_variant	8/8	1	NM_000042.3	P1
APOH	ENST00000585162.1	c.*21C>T		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99054 AN: 151988 Hom.: 33640 Cov.: 33

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.600

GnomAD3 exomes AF: 0.626 AC: 156499 AN: 250168 Hom.: 50937 AF XY: 0.616 AC XY: 83251 AN XY: 135172

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.930

Gnomad SAS exome AF: 0.677

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.580 AC: 837844 AN: 1443614 Hom.: 249828 Cov.: 27 AF XY: 0.581 AC XY: 417863 AN XY: 718936

Gnomad4 AFR exome AF: 0.841

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.652 AC: 99185 AN: 152106 Hom.: 33707 Cov.: 33 AF XY: 0.653 AC XY: 48523 AN XY: 74338

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.606

Alfa AF: 0.568 Hom.: 35251

Bravo AF: 0.665

Asia WGS AF: 0.799 AC: 2779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6933; hg19: chr17-64208230;