17-66251554-T-G

Variant names:

• chr17-66251554-T-G
• rs8073418
• ENST00000577982.1:c.-44+4852A>C

Variant summary

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

The ENST00000577982.1(APOH):​c.-44+4852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,042 control chromosomes in the GnomAD database, including 12,452 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 0.39 (12452 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 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.-44+4852A>C		intron	N/A	ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59755 AN: 151924 Hom.: 12442 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.393 AC: 59809 AN: 152042 Hom.: 12452 Cov.: 32 AF XY: 0.388 AC XY: 28845 AN XY: 74330

African (AFR) AF: 0.506 AC: 20987 AN: 41466

American (AMR) AF: 0.405 AC: 6168 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3472

East Asian (EAS) AF: 0.117 AC: 606 AN: 5188

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3256 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25157 AN: 67962

Other (OTH) AF: 0.334 AC: 707 AN: 2116

Alfa AF: 0.363 Hom.: 7737

Bravo AF: 0.404

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.1
DANN	Benign	0.39
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs8073418; hg19: chr17-64247672;