chr17-66215855-G-A

Variant names:

• chr17-66215855-G-A
• rs2873966
• NM_000042.3:c.784+933C>T

Variant summary

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

The NM_000042.3(APOH):​c.784+933C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,000 control chromosomes in the GnomAD database, including 4,613 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 0.23 (4613 hom., cov: 32)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.784+933C>T		intron_variant	Intron 6 of 7	ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.784+933C>T		intron_variant	Intron 6 of 7	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000585162.1	c.256+933C>T		intron_variant	Intron 2 of 2	2		ENSP00000462260.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35559 AN: 151882 Hom.: 4612 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.234 AC: 35579 AN: 152000 Hom.: 4613 Cov.: 32 AF XY: 0.226 AC XY: 16799 AN XY: 74290

African (AFR) AF: 0.180 AC: 7448 AN: 41464

American (AMR) AF: 0.160 AC: 2435 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3468

East Asian (EAS) AF: 0.0915 AC: 474 AN: 5178

South Asian (SAS) AF: 0.126 AC: 608 AN: 4814

European-Finnish (FIN) AF: 0.241 AC: 2543 AN: 10554

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20458 AN: 67956

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.272 Hom.: 2337

Bravo AF: 0.226

Asia WGS AF: 0.130 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2873966; hg19: chr17-64211973;