17-66235598-T-C

Variant names:

• chr17-66235598-T-C
• rs12944940
• ENST00000577982.1:c.-43-6176A>G

Variant summary

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

The ENST00000577982.1(APOH):​c.-43-6176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,862 control chromosomes in the GnomAD database, including 9,365 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 0.32 (9365 hom., cov: 31)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 2 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 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.-43-6176A>G		intron_variant	Intron 1 of 5	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48972 AN: 151744 Hom.: 9344 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.323 AC: 49043 AN: 151862 Hom.: 9365 Cov.: 31 AF XY: 0.334 AC XY: 24789 AN XY: 74222

African (AFR) AF: 0.410 AC: 16982 AN: 41404

American (AMR) AF: 0.431 AC: 6559 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3968 AN: 5156

South Asian (SAS) AF: 0.512 AC: 2472 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2731 AN: 10524

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14633 AN: 67962

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.308 Hom.: 2506

Bravo AF: 0.339

Asia WGS AF: 0.603 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.90
PhyloP100		0.51

Splicing

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

Other links and lift over

dbSNP: rs12944940; hg19: chr17-64231716;