NM_000546.5(TP53):c.474C>T (p.Arg158=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Jun 15, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000424020.3

Allele description [Variation Report for NM_000546.5(TP53):c.474C>T (p.Arg158=)]

NM_000546.5(TP53):c.474C>T (p.Arg158=)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.474C>T (p.Arg158=)
HGVS:
  • NC_000017.11:g.7675138G>A
  • NG_017013.2:g.17413C>T
  • NM_000546.5:c.474C>T
  • NM_001126112.2:c.474C>T
  • NM_001126113.2:c.474C>T
  • NM_001126114.2:c.474C>T
  • NM_001126115.1:c.78C>T
  • NM_001126116.1:c.78C>T
  • NM_001126117.1:c.78C>T
  • NM_001126118.1:c.357C>T
  • NM_001276695.2:c.357C>T
  • NM_001276696.2:c.357C>T
  • NM_001276697.2:c.-4C>T
  • NM_001276698.2:c.-4C>T
  • NM_001276699.2:c.-4C>T
  • NM_001276760.2:c.357C>T
  • NM_001276761.2:c.357C>T
  • NP_000537.3:p.Arg158=
  • NP_001119584.1:p.Arg158=
  • NP_001119585.1:p.Arg158=
  • NP_001119586.1:p.Arg158=
  • NP_001119587.1:p.Arg26=
  • NP_001119588.1:p.Arg26=
  • NP_001119589.1:p.Arg26=
  • NP_001119590.1:p.Arg119=
  • NP_001263624.1:p.Arg119=
  • NP_001263625.1:p.Arg119=
  • NP_001263689.1:p.Arg119=
  • NP_001263690.1:p.Arg119=
  • LRG_321t1:c.474C>T
  • LRG_321t2:c.474C>T
  • LRG_321t3:c.474C>T
  • LRG_321t4:c.474C>T
  • LRG_321t5:c.78C>T
  • LRG_321t6:c.78C>T
  • LRG_321t7:c.78C>T
  • LRG_321t8:c.357C>T
  • LRG_321:g.17413C>T
  • LRG_321:p.Arg158=
  • LRG_321p1:p.Arg158=
  • LRG_321p3:p.Arg158=
  • LRG_321p4:p.Arg158=
  • LRG_321p5:p.Arg26=
  • LRG_321p6:p.Arg26=
  • LRG_321p7:p.Arg26=
  • LRG_321p8:p.Arg119=
  • NC_000017.10:g.7578456G>A
  • NM_000546.4:c.474C>T
  • p.R158R
Links:
dbSNP: rs139200646
NCBI 1000 Genomes Browser:
rs139200646
Molecular consequence:
  • NM_001276697.2:c.-4C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276698.2:c.-4C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276699.2:c.-4C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.5:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126112.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126113.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126114.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126115.1:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126116.1:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126117.1:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126118.1:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276695.2:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276696.2:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276760.2:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276761.2:c.357C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000523505GeneDxcriteria provided, single submitter
Likely benign
(Oct 10, 2017)
germlineclinical testing

Citation Link,

SCV000918327Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Jun 15, 2018)
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
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.

de Andrade KC, Mirabello L, Stewart DR, Karlins E, Koster R, Wang M, Gapstur SM, Gaudet MM, Freedman ND, Landi MT, Lemonnier N, Hainaut P, Savage SA, Achatz MI.

Hum Mutat. 2017 Dec;38(12):1723-1730. doi: 10.1002/humu.23320. Epub 2017 Sep 21.

PubMed [citation]
PMID:
28861920
PMCID:
PMC6858060

Details of each submission

From GeneDx, SCV000523505.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918327.1

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

Description

Variant summary: TP53 c.474C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 11.57 fold of the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant was also found in 2/9884 individuals who are cancer-free and older than age 70, suggesting this variant is unlikely to be pathogenic. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Jun 14, 2021

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