rs2607775
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004628.5(XPC):c.-27G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,612,026 control chromosomes in the GnomAD database, including 172,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.42 ( 14100 hom., cov: 34)
Exomes 𝑓: 0.46 ( 158875 hom. )
Consequence
XPC
NM_004628.5 5_prime_UTR
NM_004628.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.90
Genes affected
XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 3-14178595-C-G is Benign according to our data. Variant chr3-14178595-C-G is described in ClinVar as [Benign]. Clinvar id is 259465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPC | NM_004628.5 | c.-27G>C | 5_prime_UTR_variant | 1/16 | ENST00000285021.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPC | ENST00000285021.12 | c.-27G>C | 5_prime_UTR_variant | 1/16 | 1 | NM_004628.5 | P1 | ||
XPC | ENST00000476581.6 | c.-27G>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | 1 | ||||
XPC | ENST00000511155.1 | c.-27G>C | 5_prime_UTR_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.421 AC: 64108AN: 152102Hom.: 14088 Cov.: 34
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GnomAD3 exomes AF: 0.415 AC: 102197AN: 246200Hom.: 22923 AF XY: 0.416 AC XY: 55820AN XY: 134194
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GnomAD4 exome AF: 0.458 AC: 669200AN: 1459806Hom.: 158875 Cov.: 45 AF XY: 0.456 AC XY: 331040AN XY: 726302
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GnomAD4 genome ? AF: 0.421 AC: 64159AN: 152220Hom.: 14100 Cov.: 34 AF XY: 0.419 AC XY: 31190AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group C Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Xeroderma pigmentosum group A Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at