13-102845848-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001204425.2(BIVM-ERCC5):c.1450+6045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 258,432 control chromosomes in the GnomAD database, including 76,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.76 ( 43735 hom., cov: 34)
Exomes 𝑓: 0.78 ( 32549 hom. )
Consequence
BIVM-ERCC5
NM_001204425.2 intron
NM_001204425.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.57
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 13-102845848-A-G is Benign according to our data. Variant chr13-102845848-A-G is described in ClinVar as [Benign]. Clinvar id is 310903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIVM-ERCC5 | NM_001204425.2 | c.1450+6045A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC5 | ENST00000535557.5 | n.8A>G | non_coding_transcript_exon_variant | 1/7 | 5 | ||||
ERCC5 | ENST00000651002.1 | c.-419A>G | 5_prime_UTR_variant, NMD_transcript_variant | 1/15 | |||||
ERCC5 | ENST00000652613.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.755 AC: 114866AN: 152044Hom.: 43702 Cov.: 34
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GnomAD4 exome AF: 0.777 AC: 82596AN: 106270Hom.: 32549 Cov.: 0 AF XY: 0.779 AC XY: 40153AN XY: 51518
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GnomAD4 genome AF: 0.755 AC: 114950AN: 152162Hom.: 43735 Cov.: 34 AF XY: 0.753 AC XY: 56042AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | This variant is associated with the following publications: (PMID: 25644244, 22982416, 22981091, 22866149, 26338418) - |
Xeroderma pigmentosum, group G Benign:1
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at