rs2215415

chr17-66219453-G-Achr17-66219453-G-T

Variant summary

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

The NM_000042.3(APOH):c.604+1101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,968 control chromosomes in the GnomAD database, including 37,619 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 (37619 hom., cov: 30)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOH	NM_000042.3	c.604+1101C>T		intron_variant		ENST00000205948.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOH	ENST00000205948.11	c.604+1101C>T		intron_variant		1	NM_000042.3	P1
APOH	ENST00000581797.5	c.424+1101C>T		intron_variant		3
APOH	ENST00000585162.1	c.77+1101C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105050 AN: 151850 Hom.: 37549 Cov.: 30

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.692 AC: 105182 AN: 151968 Hom.: 37619 Cov.: 30 AF XY: 0.693 AC XY: 51435 AN XY: 74252

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.643

Alfa AF: 0.646 Hom.: 6817

Bravo AF: 0.705

Asia WGS AF: 0.825 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.1
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2215415; hg19: chr17-64215571;