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NM_000384.3(APOB):c.409G>T (p.Glu137Ter) AND Familial hypobetalipoproteinemia 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 22, 2020
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:
RCV000470253.13

Allele description [Variation Report for NM_000384.3(APOB):c.409G>T (p.Glu137Ter)]

NM_000384.3(APOB):c.409G>T (p.Glu137Ter)

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.409G>T (p.Glu137Ter)
HGVS:
  • NC_000002.12:g.21038086C>A
  • NG_011793.1:g.10988G>T
  • NM_000384.3:c.409G>TMANE SELECT
  • NP_000375.3:p.Glu137Ter
  • NC_000002.11:g.21260958C>A
  • NM_000384.2:c.409G>T
  • NM_000384.3(APOB):c.409G>TMANE SELECT
  • p.Glu137Ter
Protein change:
E137*
Links:
dbSNP: rs766243954
NCBI 1000 Genomes Browser:
rs766243954
Molecular consequence:
  • NM_000384.3:c.409G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001422761Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 22, 2020) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001422761.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The p.Glu137Ter variant in APOB has not been previously reported in individuals with low LDL, but has been identified in 0.006483% (1/15424) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs766243954). This variant has also been reported in ClinVar (VariationID: 404400) as pathogenic by Invitae and Fulgent Genetics. This nonsense variant leads to a premature termination codon at position 137, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the APOB gene is an established disease mechanism in low LDL. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Glu137Ter variant is uncertain. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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

Last Updated: Apr 20, 2024