19-44907187-G-A

Variant summary

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

The NM_000041.4(APOE):c.43+520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 193,920 control chromosomes in the GnomAD database, including 14,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (11839 hom., cov: 32)
  • Exomes 𝑓: 0.35 (2818 hom.)
• Consequence: APOE NM_000041.4 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.757

Genes affected

APOE (HGNC:613): (apolipoprotein E) The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOE	NM_000041.4	c.43+520G>A		intron_variant		ENST00000252486.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOE	ENST00000252486.9	c.43+520G>A		intron_variant		1	NM_000041.4	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59281 AN: 151866 Hom.: 11834 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.351 AC: 14727 AN: 41934 Hom.: 2818 Cov.: 0 AF XY: 0.351 AC XY: 7693 AN XY: 21930

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.390 AC: 59316 AN: 151986 Hom.: 11839 Cov.: 32 AF XY: 0.391 AC XY: 29034 AN XY: 74282

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.404

Alfa AF: 0.397 Hom.: 8417

Bravo AF: 0.375

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Warfarin response Other:1

drug response, no assertion criteria provided

research

Pharmacogenomics Lab, Chungbuk National University

Aug 31, 2010

- likely responsive

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.54

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: rs769450; hg19: chr19-45410444;