2-21003346-GAAA-GAAAAA

Position:

• chr2-21003346-GAAA-GAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000384.3(APOB):​c.12088-14_12088-13dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,259,118 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: APOB NM_000384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOB	NM_000384.3	c.12088-14_12088-13dupTT		intron_variant		ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.12088-14_12088-13dupTT		intron_variant		1	NM_000384.3	ENSP00000233242.1

Frequencies

GnomAD3 genomes AF: 0.00000727 AC: 1 AN: 137624 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000282 AC: 4 AN: 141744 Hom.: 0 AF XY: 0.0000388 AC XY: 3 AN XY: 77222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000214

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000194

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000303 AC: 34 AN: 1121494 Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 23 AN XY: 557464

Gnomad4 AFR exome AF: 0.0000402

Gnomad4 AMR exome AF: 0.0000306

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000468

Gnomad4 FIN exome AF: 0.0000271

Gnomad4 NFE exome AF: 0.0000278

Gnomad4 OTH exome AF: 0.0000658

GnomAD4 genome AF: 0.00000727 AC: 1 AN: 137624 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 1 AN XY: 66394

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000127

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs751121092; hg19: chr2-21226218;