17-66213160-C-G

Variant names:

• chr17-66213160-C-G
• rs4790914
• NM_000042.3:c.983-972G>C

Variant summary

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

The NM_000042.3(APOH):​c.983-972G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,126 control chromosomes in the GnomAD database, including 35,572 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 0.68 (35572 hom., cov: 33)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	NM_000042.3	MANE Select	c.983-972G>C		intron	N/A	NP_000033.2	A0A384NKM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000205948.11	TSL:1 MANE Select	c.983-972G>C		intron	N/A	ENSP00000205948.6	P02749
	APOH	ENST00000879124.1		c.983-972G>C		intron	N/A	ENSP00000549183.1
	APOH	ENST00000879112.1		c.980-972G>C		intron	N/A	ENSP00000549171.1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102612 AN: 152008 Hom.: 35510 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.675 AC: 102738 AN: 152126 Hom.: 35572 Cov.: 33 AF XY: 0.676 AC XY: 50275 AN XY: 74372

African (AFR) AF: 0.805 AC: 33412 AN: 41504

American (AMR) AF: 0.663 AC: 10132 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4731 AN: 5164

South Asian (SAS) AF: 0.743 AC: 3582 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6075 AN: 10582

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40778 AN: 67988

Other (OTH) AF: 0.628 AC: 1326 AN: 2110

Alfa AF: 0.651 Hom.: 4039

Bravo AF: 0.686

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.43
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: rs4790914; hg19: chr17-64209278;