chr17-66251554-T-G

Position:

• chr17-66251554-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000577982.1	c.-44+4852A>C		intron_variant		5		ENSP00000464301

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

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.334

Alfa AF: 0.355 Hom.: 5496

Bravo AF: 0.404

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8073418; hg19: chr17-64247672;