rs2215413

chr17-66253379-T-G

Variant summary

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

The ENST00000577982.1(APOH):c.-44+3027A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,760 control chromosomes in the GnomAD database, including 15,758 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 0.45 (15758 hom., cov: 31)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000577982.1	c.-44+3027A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67735 AN: 151642 Hom.: 15738 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.447 AC: 67793 AN: 151760 Hom.: 15758 Cov.: 31 AF XY: 0.440 AC XY: 32633 AN XY: 74146

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.382

Alfa AF: 0.417 Hom.: 14627

Bravo AF: 0.457

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.9
Dann	Benign	0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2215413; hg19: chr17-64249497;