chr17-66212112-G-A

Variant names:

• chr17-66212112-G-A
• rs6933
• NM_000042.3:c.*21C>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.*21C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,595,720 control chromosomes in the GnomAD database, including 283,535 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 0.65 (33707 hom., cov: 33)
  • Exomes 𝑓: 0.58 (249828 hom.)
• Consequence: APOH NM_000042.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 23 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 (EAS) allele frequency at 95% confidence interval = 0.907 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	NM_000042.3	MANE Select	c.*21C>T		3_prime_UTR	Exon 8 of 8	NP_000033.2	A0A384NKM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000205948.11	TSL:1 MANE Select	c.*21C>T		3_prime_UTR	Exon 8 of 8	ENSP00000205948.6	P02749
	APOH	ENST00000879124.1		c.*21C>T		3_prime_UTR	Exon 8 of 8	ENSP00000549183.1
	APOH	ENST00000879112.1		c.*21C>T		3_prime_UTR	Exon 8 of 8	ENSP00000549171.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99054 AN: 151988 Hom.: 33640 Cov.: 33

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.600

GnomAD2 exomes AF: 0.626 AC: 156499 AN: 250168 AF XY: 0.616

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.930

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.580 AC: 837844 AN: 1443614 Hom.: 249828 Cov.: 27 AF XY: 0.581 AC XY: 417863 AN XY: 718936

African (AFR) AF: 0.841 AC: 27845 AN: 33118

American (AMR) AF: 0.677 AC: 30148 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11804 AN: 26008

East Asian (EAS) AF: 0.950 AC: 37583 AN: 39570

South Asian (SAS) AF: 0.679 AC: 58115 AN: 85568

European-Finnish (FIN) AF: 0.552 AC: 29472 AN: 53360

Middle Eastern (MID) AF: 0.463 AC: 2659 AN: 5738

European-Non Finnish (NFE) AF: 0.552 AC: 604965 AN: 1095978

Other (OTH) AF: 0.590 AC: 35253 AN: 59750

GnomAD4 genome AF: 0.652 AC: 99185 AN: 152106 Hom.: 33707 Cov.: 33 AF XY: 0.653 AC XY: 48523 AN XY: 74338

African (AFR) AF: 0.826 AC: 34299 AN: 41520

American (AMR) AF: 0.637 AC: 9724 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1607 AN: 3466

East Asian (EAS) AF: 0.929 AC: 4810 AN: 5178

South Asian (SAS) AF: 0.697 AC: 3359 AN: 4820

European-Finnish (FIN) AF: 0.540 AC: 5710 AN: 10572

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37646 AN: 67982

Other (OTH) AF: 0.606 AC: 1278 AN: 2110

Alfa AF: 0.577 Hom.: 45729

Bravo AF: 0.665

Asia WGS AF: 0.799 AC: 2779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.42
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6933; hg19: chr17-64208230;