ENST00000577982.1:c.-43-6482G>A

Variant names:

• chr17-66235904-C-T
• rs7215391
• ENST00000577982.1:c.-43-6482G>A

Variant summary

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

The ENST00000577982.1(APOH):​c.-43-6482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,146 control chromosomes in the GnomAD database, including 3,660 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 0.21 (3660 hom., cov: 32)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 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.-43-6482G>A		intron_variant	Intron 1 of 5	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32082 AN: 151034 Hom.: 3660 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.212 AC: 32103 AN: 151146 Hom.: 3660 Cov.: 32 AF XY: 0.204 AC XY: 15071 AN XY: 73798

African (AFR) AF: 0.209 AC: 8600 AN: 41148

American (AMR) AF: 0.138 AC: 2091 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3468

East Asian (EAS) AF: 0.0631 AC: 324 AN: 5136

South Asian (SAS) AF: 0.0718 AC: 344 AN: 4794

European-Finnish (FIN) AF: 0.207 AC: 2128 AN: 10300

Middle Eastern (MID) AF: 0.111 AC: 32 AN: 288

European-Non Finnish (NFE) AF: 0.256 AC: 17397 AN: 67880

Other (OTH) AF: 0.179 AC: 376 AN: 2100

Alfa AF: 0.240 Hom.: 571

Bravo AF: 0.208

Asia WGS AF: 0.0770 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs7215391; hg19: chr17-64232022;