rs16958979

Variant names:

• chr17-66227741-C-T
• rs16958979
• NM_000042.3:c.241+279G>A

Variant summary

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

The NM_000042.3(APOH):​c.241+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,134 control chromosomes in the GnomAD database, including 808 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 0.093 (808 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 5 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 = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000042.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	NM_000042.3	MANE Select	c.241+279G>A		intron	N/A	NP_000033.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000205948.11	TSL:1 MANE Select	c.241+279G>A		intron	N/A	ENSP00000205948.6
	APOH	ENST00000581797.5	TSL:3	c.61+279G>A		intron	N/A	ENSP00000463553.1
	APOH	ENST00000577982.1	TSL:5	c.241+279G>A		intron	N/A	ENSP00000464301.1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14159 AN: 152016 Hom.: 803 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0855

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

GnomAD4 genome AF: 0.0932 AC: 14184 AN: 152134 Hom.: 808 Cov.: 31 AF XY: 0.0924 AC XY: 6871 AN XY: 74376

African (AFR) AF: 0.165 AC: 6860 AN: 41458

American (AMR) AF: 0.0573 AC: 876 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5178

South Asian (SAS) AF: 0.0586 AC: 283 AN: 4826

European-Finnish (FIN) AF: 0.0895 AC: 948 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4400 AN: 68008

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0875 Hom.: 100

Bravo AF: 0.0935

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.33
PhyloP100		0.010
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: rs16958979; hg19: chr17-64223859;