chr17-66244619-C-G

Variant names:

• chr17-66244619-C-G
• rs16959003
• ENST00000577982.1:c.-44+11787G>C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• 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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0539

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.154

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16959003; hg19: chr17-64240737;