NM_000042.3:c.784+733C>A

Variant names:

• chr17-66216055-G-T
• rs8178857
• NM_000042.3:c.784+733C>A

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+733C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,796 control chromosomes in the GnomAD database, including 909 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 0.11 (909 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.784+733C>A		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+733C>A		intron_variant	Intron 6 of 7	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000585162.1	c.256+733C>A		intron_variant	Intron 2 of 2	2		ENSP00000462260.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16332 AN: 151678 Hom.: 907 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.108 AC: 16346 AN: 151796 Hom.: 909 Cov.: 31 AF XY: 0.107 AC XY: 7920 AN XY: 74144

African (AFR) AF: 0.112 AC: 4620 AN: 41378

American (AMR) AF: 0.0743 AC: 1131 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3466

East Asian (EAS) AF: 0.0895 AC: 462 AN: 5162

South Asian (SAS) AF: 0.109 AC: 525 AN: 4802

European-Finnish (FIN) AF: 0.127 AC: 1338 AN: 10528

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7420 AN: 67916

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.111 Hom.: 147

Bravo AF: 0.103

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.44
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8178857; hg19: chr17-64212173;