rs4781563
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005236.3(ERCC4):c.*3195G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 211,784 control chromosomes in the GnomAD database, including 6,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.23 ( 4512 hom., cov: 32)
Exomes 𝑓: 0.27 ( 2158 hom. )
Consequence
ERCC4
NM_005236.3 3_prime_UTR
NM_005236.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.504
Genes affected
ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 16-13951542-G-A is Benign according to our data. Variant chr16-13951542-G-A is described in ClinVar as [Benign]. Clinvar id is 317868.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.*3195G>A | 3_prime_UTR_variant | 11/11 | ENST00000311895.8 | ||
ERCC4 | XM_011522424.4 | c.*3195G>A | 3_prime_UTR_variant | 12/12 | |||
ERCC4 | XM_011522427.2 | c.*3195G>A | 3_prime_UTR_variant | 6/6 | |||
ERCC4 | XM_047433774.1 | c.*3195G>A | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.*3195G>A | 3_prime_UTR_variant | 11/11 | 1 | NM_005236.3 | P1 | ||
ERCC4 | ENST00000682617.1 | c.*3195G>A | 3_prime_UTR_variant | 12/12 |
Frequencies
GnomAD3 genomes ? AF: 0.234 AC: 35602AN: 151894Hom.: 4508 Cov.: 32
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GnomAD4 exome AF: 0.265 AC: 15857AN: 59770Hom.: 2158 Cov.: 0 AF XY: 0.270 AC XY: 7515AN XY: 27816
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GnomAD4 genome ? AF: 0.234 AC: 35626AN: 152014Hom.: 4512 Cov.: 32 AF XY: 0.232 AC XY: 17223AN XY: 74308
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group F Benign:1
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. - |
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