rs3785617

Positions:

• chr17-66222897-T-C
• chr17-66222897-T-G

Variant summary

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

The NM_000042.3(APOH):​c.415+801A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,008 control chromosomes in the GnomAD database, including 7,552 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 0.31 (7552 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOH	NM_000042.3	c.415+801A>G		intron_variant		ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.415+801A>G		intron_variant		1	NM_000042.3	ENSP00000205948	P1
APOH	ENST00000577982.1	c.415+801A>G		intron_variant		5		ENSP00000464301
APOH	ENST00000581797.5	c.235+801A>G		intron_variant		3		ENSP00000463553

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46927 AN: 151890 Hom.: 7542 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.309 AC: 46968 AN: 152008 Hom.: 7552 Cov.: 31 AF XY: 0.301 AC XY: 22339 AN XY: 74304

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.280

Alfa AF: 0.343 Hom.: 9033

Bravo AF: 0.300

Asia WGS AF: 0.188 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.26

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: rs3785617; hg19: chr17-64219015;