17-66244619-C-G

Variant names:

• chr17-66244619-C-G
• rs16959003
• ENST00000577982.1:c.-44+11787G>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+11787G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,056 control chromosomes in the GnomAD database, including 3,105 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 0.18 (3105 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000577982.1	c.-44+11787G>C		intron_variant	Intron 1 of 5	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27290 AN: 151936 Hom.: 3103 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.180 AC: 27317 AN: 152056 Hom.: 3105 Cov.: 32 AF XY: 0.183 AC XY: 13599 AN XY: 74340

African (AFR) AF: 0.290 AC: 12031 AN: 41454

American (AMR) AF: 0.270 AC: 4118 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.0539 AC: 279 AN: 5180

South Asian (SAS) AF: 0.266 AC: 1279 AN: 4802

European-Finnish (FIN) AF: 0.107 AC: 1132 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7665 AN: 67990

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.0495 Hom.: 44

Bravo AF: 0.194

Asia WGS AF: 0.178 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.41
PhyloP100		-0.011

Splicing

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

Other links and lift over

dbSNP: rs16959003; hg19: chr17-64240737;