rs8178835

Positions:

• chr17-66224132-A-G
• chr17-66224132-A-T

Variant summary

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

The NM_000042.3(APOH):​c.339-358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,068 control chromosomes in the GnomAD database, including 10,283 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 0.34 (10283 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOH	NM_000042.3	c.339-358T>C		intron_variant		ENST00000205948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000205948.11	c.339-358T>C		intron_variant		1	NM_000042.3	P1
APOH	ENST00000577982.1	c.339-358T>C		intron_variant		5
APOH	ENST00000581797.5	c.159-358T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51795 AN: 151950 Hom.: 10263 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.341 AC: 51858 AN: 152068 Hom.: 10283 Cov.: 31 AF XY: 0.351 AC XY: 26123 AN XY: 74330

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.333

Alfa AF: 0.271 Hom.: 3484

Bravo AF: 0.358

Asia WGS AF: 0.620 AC: 2152 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	3.0
DANN	Benign	0.61

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: rs8178835; hg19: chr17-64220250;