rs1193057149

chr2-21003344-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000384.3(APOB):c.12088-10C>T variant causes a splice polypyrimidine tract, 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 0.000075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOB NM_000384.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002305
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.233

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-21003344-G-A is Benign according to our data. Variant chr2-21003344-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 477796.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOB	NM_000384.3	c.12088-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000233242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOB	ENST00000233242.5	c.12088-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000384.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 147070 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000500

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: 0.000759

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000260 AC: 372 AN: 1432208 Hom.: 0 Cov.: 34 AF XY: 0.000240 AC XY: 171 AN XY: 712664

Gnomad4 AFR exome AF: 0.00251

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.000592

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.000294

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.000406

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000748 AC: 11 AN: 147070 Hom.: 0 Cov.: 32 AF XY: 0.0000840 AC XY: 6 AN XY: 71392

Gnomad4 AFR AF: 0.0000500

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000759

Gnomad4 NFE AF: 0.0000300

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00439 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 24, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.0
Dann	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.058
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

Other links and lift over

dbSNP: rs1193057149; hg19: chr2-21226216;