chr17-66223079-G-A

Variant names:

• chr17-66223079-G-A
• rs8178841
• NM_000042.3:c.415+619C>T

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+619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 152,184 control chromosomes in the GnomAD database, including 327 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 0.066 (327 hom., cov: 32)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.415+619C>T		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+619C>T		intron_variant	Intron 4 of 7	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000581797.5	c.235+619C>T		intron_variant	Intron 4 of 5	3		ENSP00000463553.1
APOH	ENST00000577982.1	c.415+619C>T		intron_variant	Intron 5 of 5	5		ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10104 AN: 152066 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0665 AC: 10115 AN: 152184 Hom.: 327 Cov.: 32 AF XY: 0.0664 AC XY: 4942 AN XY: 74398

African (AFR) AF: 0.0742 AC: 3079 AN: 41504

American (AMR) AF: 0.0453 AC: 693 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3468

East Asian (EAS) AF: 0.0637 AC: 329 AN: 5166

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4824

European-Finnish (FIN) AF: 0.0888 AC: 941 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0643 AC: 4371 AN: 68012

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0634 Hom.: 201

Bravo AF: 0.0627

Asia WGS AF: 0.0590 AC: 203 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	1.8
DANN	Benign	0.32
PhyloP100		-0.71
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: rs8178841; hg19: chr17-64219197;