Variant 2-21003346-GAAA-GAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000384.3(APOB):c.12088-13delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,174,020 control chromosomes in the GnomAD database, including 31 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 32)

Exomes 𝑓: 0.013 ( 26 hom. )

Consequence

APOB
NM_000384.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.342

Variant links:

Genes affected

APOB (HGNC:603): (apolipoprotein B) This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [provided by RefSeq, Dec 2019]

APOB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-21003346-GA-G is Benign according to our data. Variant chr2-21003346-GA-G is described in ClinVar as [Benign]. Clinvar id is 490382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-21003346-GA-G is described in Lovd as [Benign]. Variant chr2-21003346-GA-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOB	NM_000384.3 linkuse as main transcript	c.12088-13delT		intron_variant		ENST00000233242.5	NP_000375.3	P04114Q7Z7Q0Q59HB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5 linkuse as main transcript	c.12088-13delT		intron_variant		1	NM_000384.3	ENSP00000233242.1		P04114

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

491

AN:

137524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00232

Gnomad ASJ

AF:

0.00646

Gnomad EAS

AF:

0.0425

Gnomad SAS

AF:

0.00272

Gnomad FIN

AF:

0.000509

Gnomad MID

AF:

0.0105

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00789

GnomAD3 exomes

AF:

0.0184

AC:

2615

AN:

141744

Hom.:

AF XY:

0.0180

AC XY:

1392

AN XY:

77222

show subpopulations

Gnomad AFR exome

AF:

0.00527

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.0830

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0134

AC:

13904

AN:

1036430

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

6722

AN XY:

513868

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.0540

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.00358

AC:

493

AN:

137590

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

252

AN XY:

66410

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00231

Gnomad4 ASJ

AF:

0.00646

Gnomad4 EAS

AF:

0.0426

Gnomad4 SAS

AF:

0.00273

Gnomad4 FIN

AF:

0.000509

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.00782

Bravo

AF:

0.00370

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Hypercholesterolemia, familial, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Aug 28, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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