NM_000042.3:c.604+1274C>A

Variant names:

• chr17-66219280-G-T
• rs7212060
• NM_000042.3:c.604+1274C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000042.3(APOH):​c.604+1274C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,850 control chromosomes in the GnomAD database, including 17,506 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 0.45 (17506 hom., cov: 31)
• Consequence: APOH NM_000042.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOH	NM_000042.3	c.604+1274C>A		intron_variant	Intron 5 of 7	ENST00000205948.11	NP_000033.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOH	ENST00000205948.11	c.604+1274C>A		intron_variant	Intron 5 of 7	1	NM_000042.3	ENSP00000205948.6
APOH	ENST00000581797.5	c.424+1274C>A		intron_variant	Intron 5 of 5	3		ENSP00000463553.1
APOH	ENST00000585162.1	c.76+1274C>A		intron_variant	Intron 1 of 2	2		ENSP00000462260.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67951 AN: 151730 Hom.: 17462 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.448 AC: 68058 AN: 151850 Hom.: 17506 Cov.: 31 AF XY: 0.457 AC XY: 33902 AN XY: 74218

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.427

Alfa AF: 0.271 Hom.: 840

Bravo AF: 0.468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs7212060; hg19: chr17-64215398;