rs11867410

Variant names:

• chr17-66231245-T-C
• rs11867410
• ENST00000577982.1:c.-43-1823A>G

Variant summary

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

The ENST00000577982.1(APOH):​c.-43-1823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,164 control chromosomes in the GnomAD database, including 153 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 0.040 (153 hom., cov: 31)
• Consequence: APOH ENST00000577982.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577982.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOH	ENST00000577982.1	TSL:5	c.-43-1823A>G		intron	N/A	ENSP00000464301.1	J3QRN2

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6139 AN: 152046 Hom.: 153 Cov.: 31

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0393

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

GnomAD4 genome AF: 0.0404 AC: 6141 AN: 152164 Hom.: 153 Cov.: 31 AF XY: 0.0403 AC XY: 2994 AN XY: 74382

African (AFR) AF: 0.0337 AC: 1400 AN: 41536

American (AMR) AF: 0.0285 AC: 435 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 191 AN: 3468

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5178

South Asian (SAS) AF: 0.0599 AC: 288 AN: 4812

European-Finnish (FIN) AF: 0.0389 AC: 412 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0451 AC: 3063 AN: 67980

Other (OTH) AF: 0.0393 AC: 83 AN: 2110

Alfa AF: 0.0420 Hom.: 51

Bravo AF: 0.0390

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.52
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11867410;

hg19: chr17-64227363;

COSMIC: COSV52772702;