rs4253231
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000124.4(ERCC6):c.*53T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,557,202 control chromosomes in the GnomAD database, including 9,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 888 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8535 hom. )
Consequence
ERCC6
NM_000124.4 3_prime_UTR
NM_000124.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.478
Genes affected
ERCC6 (HGNC:3438): (ERCC excision repair 6, chromatin remodeling factor) This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]
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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 10-49458762-A-G is Benign according to our data. Variant chr10-49458762-A-G is described in ClinVar as [Benign]. Clinvar id is 300031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.*53T>C | 3_prime_UTR_variant | 21/21 | ENST00000355832.10 | ||
ERCC6 | NM_001346440.2 | c.*53T>C | 3_prime_UTR_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.*53T>C | 3_prime_UTR_variant | 21/21 | 1 | NM_000124.4 | P1 | ||
ENST00000423283.1 | n.235-13941A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.103 AC: 15609AN: 152140Hom.: 882 Cov.: 32
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GnomAD4 exome AF: 0.103 AC: 144284AN: 1404944Hom.: 8535 Cov.: 24 AF XY: 0.104 AC XY: 73369AN XY: 702242
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GnomAD4 genome ? AF: 0.103 AC: 15637AN: 152258Hom.: 888 Cov.: 32 AF XY: 0.105 AC XY: 7819AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
COFS syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Cockayne syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Macular degeneration Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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