rs16958979

Positions:

• chr17-66227741-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000042.3(APOH):​c.241+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,134 control chromosomes in the GnomAD database, including 808 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 0.093 (808 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOH	NM_000042.3	c.241+279G>A		intron_variant		ENST00000205948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000205948.11	c.241+279G>A		intron_variant		1	NM_000042.3	P1
APOH	ENST00000577982.1	c.241+279G>A		intron_variant		5
APOH	ENST00000581797.5	c.61+279G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14159 AN: 152016 Hom.: 803 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0855

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

GnomAD4 genome AF: 0.0932 AC: 14184 AN: 152134 Hom.: 808 Cov.: 31 AF XY: 0.0924 AC XY: 6871 AN XY: 74376

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0847 Hom.: 88

Bravo AF: 0.0935

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs16958979; hg19: chr17-64223859;