Variant chr19-44906322-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000041.4(APOE):c.-23-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.029 ( 29 hom., cov: 17)

Exomes 𝑓: 0.019 ( 69 hom. )

Consequence

APOE
NM_000041.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.685

Variant links:

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]

APOE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-44906322-C-T is Benign according to our data. Variant chr19-44906322-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1329718.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44906322-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0291 (1955/67166) while in subpopulation NFE AF= 0.0416 (1543/37048). AF 95% confidence interval is 0.0399. There are 29 homozygotes in gnomad4. There are 860 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
APOE	NM_000041.4 linkuse as main transcript	c.-23-280C>T	intron_variant	ENST00000252486.9
APOE	NM_001302688.2 linkuse as main transcript	c.56-280C>T	intron_variant
APOE	NM_001302689.2 linkuse as main transcript	c.-24+278C>T	intron_variant
APOE	NM_001302691.2 linkuse as main transcript	c.-38-265C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOE	ENST00000252486.9 linkuse as main transcript	c.-23-280C>T		intron_variant		1	NM_000041.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

1955

AN:

67120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00843

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000477

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.0412

Gnomad MID

AF:

0.0116

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0191

GnomAD4 exome

AF:

0.0188

AC:

6656

AN:

354092

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

3371

AN XY:

186710

show subpopulations

Gnomad4 AFR exome

AF:

0.00298

Gnomad4 AMR exome

AF:

0.00660

Gnomad4 ASJ exome

AF:

0.00726

Gnomad4 EAS exome

AF:

0.0000422

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0253

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0291

AC:

1955

AN:

67166

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

860

AN XY:

30242

show subpopulations

Gnomad4 AFR

AF:

0.00841

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000477

Gnomad4 SAS

AF:

0.0243

Gnomad4 FIN

AF:

0.0412

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.1

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over