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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_000384.3(APOB):c.12088-13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 1,091,966 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.033 ( 3 hom. )

Consequence

APOB
NM_000384.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

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 -9 ACMG points.

BP6

Variant 2-21003346-G-GA is Benign according to our data. Variant chr2-21003346-G-GA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 334083.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0327 (31172/954370) while in subpopulation SAS AF= 0.0438 (2272/51848). AF 95% confidence interval is 0.0423. There are 3 homozygotes in gnomad4_exome. There are 14969 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 SD gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

142

AN:

137534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000695

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00249

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.000127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000318

Gnomad OTH

AF:

0.000526

GnomAD3 exomes

AF:

0.0126

AC:

1788

AN:

141744

Hom.:

AF XY:

0.0137

AC XY:

1055

AN XY:

77222

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00669

Gnomad SAS exome

AF:

0.0383

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.00695

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0327

AC:

31172

AN:

954370

Hom.:

Cov.:

AF XY:

0.0317

AC XY:

14969

AN XY:

471794

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.0438

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0342

Gnomad4 OTH exome

AF:

0.0318

GnomAD4 genome

AF:

0.00104

AC:

143

AN:

137596

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

AN XY:

66416

show subpopulations

Gnomad4 AFR

AF:

0.000720

Gnomad4 AMR

AF:

0.000723

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00249

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.000127

Gnomad4 NFE

AF:

0.000318

Gnomad4 OTH

AF:

0.000521

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial hypobetalipoproteinemia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

- -

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