chr17-66240200-T-C

Variant names:

• chr17-66240200-T-C
• rs10048158
• ENST00000577982.1:c.-43-10778A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000577982.1(APOH):​c.-43-10778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,052 control chromosomes in the GnomAD database, including 37,369 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 0.69 (37369 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577982.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000577982.1	TSL:5	c.-43-10778A>G		intron	N/A	ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104231 AN: 151932 Hom.: 37294 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.686 AC: 104371 AN: 152052 Hom.: 37369 Cov.: 32 AF XY: 0.687 AC XY: 51042 AN XY: 74302

African (AFR) AF: 0.883 AC: 36654 AN: 41518

American (AMR) AF: 0.662 AC: 10110 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1683 AN: 3466

East Asian (EAS) AF: 0.923 AC: 4776 AN: 5172

South Asian (SAS) AF: 0.686 AC: 3307 AN: 4822

European-Finnish (FIN) AF: 0.591 AC: 6223 AN: 10534

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39469 AN: 67960

Other (OTH) AF: 0.635 AC: 1344 AN: 2116

Alfa AF: 0.625 Hom.: 54416

Bravo AF: 0.700

Asia WGS AF: 0.810 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs10048158; hg19: chr17-64236318;