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NM_000384.3(APOB):c.12696T>A (p.Tyr4232Ter) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 10, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002534034.4

Allele description [Variation Report for NM_000384.3(APOB):c.12696T>A (p.Tyr4232Ter)]

NM_000384.3(APOB):c.12696T>A (p.Tyr4232Ter)

Gene:
APOB:apolipoprotein B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p24.1
Genomic location:
Preferred name:
NM_000384.3(APOB):c.12696T>A (p.Tyr4232Ter)
HGVS:
  • NC_000002.12:g.21002726A>T
  • NG_011793.1:g.46348T>A
  • NM_000384.3:c.12696T>AMANE SELECT
  • NP_000375.3:p.Tyr4232Ter
  • NC_000002.11:g.21225598A>T
  • NM_000384.2:c.12696T>A
Protein change:
Y4232*
Links:
dbSNP: rs1466172660
NCBI 1000 Genomes Browser:
rs1466172660
Molecular consequence:
  • NM_000384.3:c.12696T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hypercholesterolemia, autosomal dominant, type B (FHCL2)
Synonyms:
APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE; APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE; HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007751; MedGen: C1704417; OMIM: 144010
Name:
Familial hypobetalipoproteinemia 1
Synonyms:
Hypobetalipoproteinemia, normotriglyceridemic; Acanthocytosis with hypobetalipoproteinemia
Identifiers:
MONDO: MONDO:0014252; MedGen: C4551990; OMIM: 615558

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003249625Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 10, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Risk of Premature Atherosclerotic Disease in Patients With Monogenic Versus Polygenic Familial Hypercholesterolemia.

Trinder M, Li X, DeCastro ML, Cermakova L, Sadananda S, Jackson LM, Azizi H, Mancini GBJ, Francis GA, Frohlich J, Brunham LR.

J Am Coll Cardiol. 2019 Jul 30;74(4):512-522. doi: 10.1016/j.jacc.2019.05.043.

PubMed [citation]
PMID:
31345425

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003249625.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Tyr4232*) in the APOB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 332 amino acid(s) of the APOB protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 31345425). ClinVar contains an entry for this variant (Variation ID: 628375). This variant disrupts a region of the APOB protein in which other variant(s) (p.Tyr4380*) have been observed in individuals with APOB-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024