rs4150314
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000123.4(ERCC5):c.960C>T(p.Asp320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,120 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0093 ( 13 hom., cov: 33)
Exomes 𝑓: 0.012 ( 118 hom. )
Consequence
ERCC5
NM_000123.4 synonymous
NM_000123.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.375
Genes affected
ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 13-102862109-C-T is Benign according to our data. Variant chr13-102862109-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 522357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102862109-C-T is described in Lovd as [Benign]. Variant chr13-102862109-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.375 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00928 (1413/152232) while in subpopulation AMR AF= 0.018 (276/15296). AF 95% confidence interval is 0.0163. There are 13 homozygotes in gnomad4. There are 721 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC5 | NM_000123.4 | c.960C>T | p.Asp320= | synonymous_variant | 8/15 | ENST00000652225.2 | |
BIVM-ERCC5 | NM_001204425.2 | c.2322C>T | p.Asp774= | synonymous_variant | 16/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC5 | ENST00000652225.2 | c.960C>T | p.Asp320= | synonymous_variant | 8/15 | NM_000123.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00928 AC: 1412AN: 152114Hom.: 13 Cov.: 33
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GnomAD3 exomes AF: 0.00986 AC: 2478AN: 251272Hom.: 13 AF XY: 0.00989 AC XY: 1343AN XY: 135828
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GnomAD4 exome AF: 0.0118 AC: 17244AN: 1461888Hom.: 118 Cov.: 32 AF XY: 0.0116 AC XY: 8436AN XY: 727248
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GnomAD4 genome ? AF: 0.00928 AC: 1413AN: 152232Hom.: 13 Cov.: 33 AF XY: 0.00969 AC XY: 721AN XY: 74434
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group G Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Aug 07, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ERCC5: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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