rs745520533

Variant names:

• chr2-21043879-CCAGCAGCAG-C
• NM_000384.3:c.58_66delCTGCTGCTG

Your query was ambiguous. Multiple possible variants found:

• chr2-21043879-CCAGCAGCAG-C
• chr2-21043879-CCAGCAGCAG-CCAG
• chr2-21043879-CCAGCAGCAG-CCAGCAG
• chr2-21043879-CCAGCAGCAG-CCAGCAGCAGCAG
• chr2-21043879-CCAGCAGCAG-CCAGCAGCAGCAGCAG
• chr2-21043879-CCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000384.3(APOB):​c.58_66delCTGCTGCTG​(p.Leu20_Leu22del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000474 in 1,265,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: APOB NM_000384.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000384.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOB	NM_000384.3	c.58_66delCTGCTGCTG	p.Leu20_Leu22del	conservative_inframe_deletion	Exon 1 of 29	ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.58_66delCTGCTGCTG	p.Leu20_Leu22del	conservative_inframe_deletion	Exon 1 of 29	1	NM_000384.3	ENSP00000233242.1
APOB	ENST00000399256.4	c.58_66delCTGCTGCTG	p.Leu20_Leu22del	conservative_inframe_deletion	Exon 1 of 17	1		ENSP00000382200.4
APOB	ENST00000673739.2	n.58_66delCTGCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 25			ENSP00000501110.2
APOB	ENST00000673882.2	n.58_66delCTGCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 23			ENSP00000501253.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000474 AC: 6 AN: 1265870 Hom.: 0 AF XY: 0.00000640 AC XY: 4 AN XY: 625010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000602

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Jan 11, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58_66delCTGCTGCTG variant (also known as p.L20_L22del) is located in coding exon 1 of the APOB gene. This variant results from an in-frame deletion of 9 nucleotides (CTGCTGCTG) at positions 58 to 66, causing a deletion of three leucine residues at codon 20 to 22. These amino acid positions are not well conserved on limited sequence alignment. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-21266751;