rs2020953
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005236.3(ERCC4):āc.2463A>Gā(p.Pro821=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,184 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0065 ( 14 hom., cov: 32)
Exomes š: 0.00069 ( 15 hom. )
Consequence
ERCC4
NM_005236.3 synonymous
NM_005236.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.66
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 16-13948059-A-G is Benign according to our data. Variant chr16-13948059-A-G is described in ClinVar as [Benign]. Clinvar id is 240123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.66 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (984/152298) while in subpopulation AFR AF= 0.0221 (920/41558). AF 95% confidence interval is 0.021. There are 14 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.2463A>G | p.Pro821= | synonymous_variant | 11/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.2601A>G | p.Pro867= | synonymous_variant | 12/12 | ||
ERCC4 | XM_047433774.1 | c.1674A>G | p.Pro558= | synonymous_variant | 8/8 | ||
ERCC4 | XM_011522427.2 | c.1113A>G | p.Pro371= | synonymous_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.2463A>G | p.Pro821= | synonymous_variant | 11/11 | 1 | NM_005236.3 | P1 | |
ERCC4 | ENST00000682617.1 | c.2601A>G | p.Pro867= | synonymous_variant | 12/12 | ||||
ERCC4 | ENST00000389138.7 | n.1740A>G | non_coding_transcript_exon_variant | 6/6 | 2 | ||||
ERCC4 | ENST00000683962.1 | c.*2157A>G | 3_prime_UTR_variant, NMD_transcript_variant | 12/12 |
Frequencies
GnomAD3 genomes ? AF: 0.00645 AC: 982AN: 152180Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00187 AC: 470AN: 251268Hom.: 6 AF XY: 0.00144 AC XY: 195AN XY: 135786
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GnomAD4 exome AF: 0.000692 AC: 1012AN: 1461886Hom.: 15 Cov.: 32 AF XY: 0.000571 AC XY: 415AN XY: 727244
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GnomAD4 genome ? AF: 0.00646 AC: 984AN: 152298Hom.: 14 Cov.: 32 AF XY: 0.00630 AC XY: 469AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Xeroderma pigmentosum, group F 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. - |
ERCC4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 16, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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