NM_000228.3(LAMB3):c.1439C>T (p.Pro480Leu) AND not specified

Clinical significance:Likely benign (Last evaluated: Jul 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001251314.1

Allele description [Variation Report for NM_000228.3(LAMB3):c.1439C>T (p.Pro480Leu)]

NM_000228.3(LAMB3):c.1439C>T (p.Pro480Leu)

Gene:
LAMB3:laminin subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.2
Genomic location:
Preferred name:
NM_000228.3(LAMB3):c.1439C>T (p.Pro480Leu)
HGVS:
  • NC_000001.11:g.209627429G>A
  • NG_007116.1:g.30047C>T
  • NM_000228.3:c.1439C>TMANE SELECT
  • NM_001017402.1:c.1439C>T
  • NM_001127641.1:c.1439C>T
  • NP_000219.2:p.Pro480Leu
  • NP_001017402.1:p.Pro480Leu
  • NP_001121113.1:p.Pro480Leu
  • NC_000001.10:g.209800774G>A
  • NM_000228.2:c.1439C>T
Protein change:
P480L
Links:
dbSNP: rs61734494
NCBI 1000 Genomes Browser:
rs61734494
Molecular consequence:
  • NM_000228.3:c.1439C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001017402.1:c.1439C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127641.1:c.1439C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001426861Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jul 17, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

A comprehensive next-generation sequencing assay for the diagnosis of epidermolysis bullosa.

Lucky AW, Dagaonkar N, Lammers K, Husami A, Kissell D, Zhang K.

Pediatr Dermatol. 2018 Mar;35(2):188-197. doi: 10.1111/pde.13392. Epub 2018 Jan 15. Erratum in: Pediatr Dermatol. 2018 Sep;35(5):732-735.

PubMed [citation]
PMID:
29334134

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001426861.1

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

Description

Variant summary: LAMB3 c.1439C>T (p.Pro480Leu) results in a non-conservative amino acid change located in the Laminin EGF domain (IPR002049) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0013 in 250774 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.9- fold the estimated maximal expected allele frequency for a pathogenic variant in LAMB3 causing Junctional Epidermolysis Bullosa phenotype (0.002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1439C>T has been reported in the literature in at least one individual affected with Epidermolysis Bullosa Simplex, however this patient had a co-occurring pathogenic variant in KRT14 (c.373C>T, p.R125C; classified pathogenic in ClinVar) that was cited as likely contributing to the patient's phenotype. This report does not provide unequivocal conclusions about association of the variant with Junctional Epidermolysis Bullosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories cited the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Jun 14, 2021

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