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NM_000726.5(CACNB4):c.44C>G (p.Pro15Arg) AND not specified

Germline classification:
Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:
Aug 12, 2020
Review status:
criteria provided, conflicting classifications
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:
RCV000186843.17

Allele description [Variation Report for NM_000726.5(CACNB4):c.44C>G (p.Pro15Arg)]

NM_000726.5(CACNB4):c.44C>G (p.Pro15Arg)

Genes:
LOC129934925:ATAC-STARR-seq lymphoblastoid silent region 12010 [Gene]
CACNB4:calcium voltage-gated channel auxiliary subunit beta 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q23.3
Genomic location:
Preferred name:
NM_000726.5(CACNB4):c.44C>G (p.Pro15Arg)
Other names:
p.P15R:CCG>CGG
HGVS:
  • NC_000002.12:g.152098968G>C
  • NG_012641.1:g.5112C>G
  • NM_000726.5:c.44C>GMANE SELECT
  • NM_001145798.2:c.44C>G
  • NP_000717.2:p.Pro15Arg
  • NP_000717.2:p.Pro15Arg
  • NP_001139270.1:p.Pro15Arg
  • NC_000002.11:g.152955482G>C
  • NM_000726.2:c.44C>G
  • NM_000726.3:c.44C>G
  • NM_000726.4:c.44C>G
Protein change:
P15R
Links:
dbSNP: rs200662010
NCBI 1000 Genomes Browser:
rs200662010
Molecular consequence:
  • NM_000726.5:c.44C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145798.2:c.44C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

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
SCV000240414GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Uncertain significance
(Dec 9, 2015)
germlineclinical testing

Citation Link,

SCV000246840Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely benign
(Apr 22, 2019)
germlineclinical testing

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

SCV000339595Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Likely benign
(Feb 8, 2016)
germlineclinical testing

Citation Link,

SCV001474893Athena Diagnostics
criteria provided, single submitter

(Athena Diagnostics Criteria)
Benign
(Aug 12, 2020)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000240414.10

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

Description

p.Pro15Arg (CCG>CGG): c.44 C>G in exon 1 of the CACNB4 gene (NM_000726.2). The P15R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports P15R was observed in 26/8128 (0.3%) alleles from individuals of European background, and the 1000 Genomes Project reports P15R was observed in 1/120 (0.8%) alleles from individuals of Mexican background, indicating it may be a rare (benign) variant in these populations. The P15R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution alters a poorly conserved position in the predicted N-terminal region of the CACNB4 protein, and disease-associated mutations have not been reported in this region to date (Escayg et al., 2000; Ohmori et al., 2008). Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s).

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

From Genetic Services Laboratory, University of Chicago, SCV000246840.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Eurofins Ntd Llc (ga), SCV000339595.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From Athena Diagnostics, SCV001474893.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 23, 2024