NM_004628.5(XPC):c.300G>A (p.Arg100=) AND not specified

Germline classification:: Benign (3 submissions)
Last evaluated:: Oct 18, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000122334.7

Allele description [Variation Report for NM_004628.5(XPC):c.300G>A (p.Arg100=)]

NM_004628.5(XPC):c.300G>A (p.Arg100=)

Gene:

XPC:XPC complex subunit, DNA damage recognition and repair factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_004628.5(XPC):c.300G>A (p.Arg100=)

HGVS:

NC_000003.12:g.14170550C>T
NG_011763.1:g.13123G>A
NM_001354726.2:c.-156G>A
NM_001354727.2:c.300G>A
NM_001354729.2:c.282G>A
NM_001354730.2:c.300G>A
NM_004628.5:c.300G>AMANE SELECT
NP_001341656.1:p.Arg100=
NP_001341658.1:p.Arg94=
NP_001341659.1:p.Arg100=
NP_004619.3:p.Arg100=
NP_004619.3:p.Arg100=
LRG_472t1:c.300G>A
LRG_472:g.13123G>A
LRG_472p1:p.Arg100=
NC_000003.11:g.14212050C>T
NM_004628.4:c.300G>A
NR_148950.2:n.333G>A
NR_148951.2:n.333G>A

Links:

dbSNP: rs2228002

NCBI 1000 Genomes Browser:

rs2228002

Molecular consequence:

NM_001354726.2:c.-156G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_148950.2:n.333G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148951.2:n.333G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001354727.2:c.300G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354729.2:c.282G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354730.2:c.300G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_004628.5:c.300G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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PLCB1 phospholipase C beta 1 [Homo sapiens]
PLCB1 phospholipase C beta 1 [Homo sapiens]
Gene ID:23236

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000086564	ITMI	no classification provided	not provided	germline	reference population	PubMed (1) [See all records that cite this PMID]
SCV000310543	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001360986	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Oct 18, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000086564

ITMI

no classification provided

not provided

germline

reference population

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

SCV000310543

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

clinical testing

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

SCV001360986

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Oct 18, 2019)

germline

clinical testing

Citation Link

Description

Please see associated publication for description of ethnicities: SCV000086564

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
African	germline	unknown	not provided	not provided	not provided	43	not provided	reference population
African_European	germline	unknown	not provided	not provided	not provided	46	not provided	reference population
Central_Asian	germline	unknown	not provided	not provided	not provided	50	not provided	reference population
East_Asian	germline	unknown	not provided	not provided	not provided	62	not provided	reference population
European	germline	unknown	not provided	not provided	not provided	331	not provided	reference population
Hispanic	germline	unknown	not provided	not provided	not provided	118	not provided	reference population
Whole_cohort	germline	unknown	not provided	not provided	not provided	681	not provided	reference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

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 ITMI, SCV000086564.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African	not provided	not provided	not provided	reference population	PubMed (1)
2	African_European	not provided	not provided	not provided	reference population	PubMed (1)
3	Central_Asian	not provided	not provided	not provided	reference population	PubMed (1)
4	East_Asian	not provided	not provided	not provided	reference population	PubMed (1)
5	European	not provided	not provided	not provided	reference population	PubMed (1)
6	Hispanic	not provided	not provided	not provided	reference population	PubMed (1)
7	Whole_cohort	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	43	not provided	discovery		not provided	0.0698	not provided	not provided
2	germline	unknown	46	not provided	discovery		not provided	0.0109	not provided	not provided
3	germline	unknown	50	not provided	discovery		not provided	0	not provided	not provided
4	germline	unknown	62	not provided	discovery		not provided	0	not provided	not provided
5	germline	unknown	331	not provided	discovery		not provided	0	not provided	not provided
6	germline	unknown	118	not provided	discovery		not provided	0.0085	not provided	not provided
7	germline	unknown	681	not provided	discovery		not provided	0.0066	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000310543.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360986.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: XPC c.300G>A (p.Arg100Arg) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0074 in 277384 control chromosomes, predominantly at a frequency of 0.079 within the African or African-American subpopulation in the gnomAD database, including 81 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 56 fold of the estimated maximal expected allele frequency for a pathogenic variant in XPC causing Xeroderma pigmentosum phenotype (0.0014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 10, 2024

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