chr17-66216124-T-C

Variant names:

• chr17-66216124-T-C
• rs4366742
• NM_000042.3:c.784+664A>G

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+664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 148,298 control chromosomes in the GnomAD database, including 36,996 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 0.69 (36996 hom., cov: 23)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	NM_000042.3	MANE Select	c.784+664A>G		intron	N/A	NP_000033.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000205948.11	TSL:1 MANE Select	c.784+664A>G		intron	N/A	ENSP00000205948.6
	APOH	ENST00000585162.1	TSL:2	c.256+664A>G		intron	N/A	ENSP00000462260.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 102919 AN: 148196 Hom.: 36926 Cov.: 23

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.695 AC: 103044 AN: 148298 Hom.: 36996 Cov.: 23 AF XY: 0.696 AC XY: 50113 AN XY: 71978

African (AFR) AF: 0.874 AC: 35087 AN: 40166

American (AMR) AF: 0.674 AC: 10023 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1807 AN: 3460

East Asian (EAS) AF: 0.914 AC: 4587 AN: 5016

South Asian (SAS) AF: 0.748 AC: 3489 AN: 4666

European-Finnish (FIN) AF: 0.574 AC: 5476 AN: 9532

Middle Eastern (MID) AF: 0.524 AC: 150 AN: 286

European-Non Finnish (NFE) AF: 0.600 AC: 40368 AN: 67322

Other (OTH) AF: 0.646 AC: 1334 AN: 2064

Alfa AF: 0.663 Hom.: 4202

Bravo AF: 0.709

Asia WGS AF: 0.825 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.79
PhyloP100		-0.72
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: rs4366742; hg19: chr17-64212242;