rs8178838

Variant names:

• chr17-66223423-T-C
• rs8178838
• NM_000042.3:c.415+275A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-66223423-T-C
• chr17-66223423-T-G

Variant summary

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

The NM_000042.3(APOH):​c.415+275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,250 control chromosomes in the GnomAD database, including 420 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 0.073 (420 hom., cov: 32)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.415+275A>G		intron_variant	Intron 4 of 7	ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.415+275A>G		intron_variant	Intron 4 of 7	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000581797.5	c.235+275A>G		intron_variant	Intron 4 of 5	3		ENSP00000463553.1
APOH	ENST00000577982.1	c.415+275A>G		intron_variant	Intron 5 of 5	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11082 AN: 152132 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0729 AC: 11095 AN: 152250 Hom.: 420 Cov.: 32 AF XY: 0.0725 AC XY: 5399 AN XY: 74440

African (AFR) AF: 0.0962 AC: 3998 AN: 41548

American (AMR) AF: 0.0474 AC: 724 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.0646 AC: 335 AN: 5188

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4824

European-Finnish (FIN) AF: 0.0893 AC: 947 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4380 AN: 68014

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

Alfa AF: 0.0642 Hom.: 386

Bravo AF: 0.0698

Asia WGS AF: 0.0590 AC: 206 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	0.79
DANN	Benign	0.53
PhyloP100		-0.33
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: rs8178838; hg19: chr17-64219541;