chr17-66214410-G-A

Variant names:

• chr17-66214410-G-A
• rs1544556
• NM_000042.3:c.982+43C>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.982+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,542,258 control chromosomes in the GnomAD database, including 40,866 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 0.17 (2790 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38076 hom.)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 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.982+43C>T		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.982+43C>T		intron	N/A	ENSP00000205948.6
	APOH	ENST00000585162.1	TSL:2	c.257-2222C>T		intron	N/A	ENSP00000462260.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25232 AN: 151830 Hom.: 2790 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.167 AC: 41269 AN: 247214 AF XY: 0.167

Gnomad AFR exome AF: 0.0450

Gnomad AMR exome AF: 0.0856

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0559

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.222 AC: 308884 AN: 1390310 Hom.: 38076 Cov.: 22 AF XY: 0.218 AC XY: 151515 AN XY: 696048

African (AFR) AF: 0.0415 AC: 1320 AN: 31806

American (AMR) AF: 0.0891 AC: 3888 AN: 43638

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3683 AN: 25612

East Asian (EAS) AF: 0.0676 AC: 2660 AN: 39326

South Asian (SAS) AF: 0.0681 AC: 5758 AN: 84498

European-Finnish (FIN) AF: 0.199 AC: 10632 AN: 53318

Middle Eastern (MID) AF: 0.113 AC: 619 AN: 5496

European-Non Finnish (NFE) AF: 0.257 AC: 269127 AN: 1048680

Other (OTH) AF: 0.193 AC: 11197 AN: 57936

GnomAD4 genome AF: 0.166 AC: 25234 AN: 151948 Hom.: 2790 Cov.: 32 AF XY: 0.160 AC XY: 11846 AN XY: 74262

African (AFR) AF: 0.0516 AC: 2135 AN: 41392

American (AMR) AF: 0.118 AC: 1808 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 501 AN: 3464

East Asian (EAS) AF: 0.0657 AC: 340 AN: 5174

South Asian (SAS) AF: 0.0645 AC: 310 AN: 4806

European-Finnish (FIN) AF: 0.202 AC: 2128 AN: 10546

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17348 AN: 67970

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.219 Hom.: 11063

Bravo AF: 0.155

Asia WGS AF: 0.0650 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-0.21
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: rs1544556; hg19: chr17-64210528;