rs148003381
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_005236.3(ERCC4):āc.906T>Cā(p.Asp302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,613,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000053 ( 0 hom. )
Consequence
ERCC4
NM_005236.3 synonymous
NM_005236.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.330
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 16-13930823-T-C is Benign according to our data. Variant chr16-13930823-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.33 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC4 | NM_005236.3 | c.906T>C | p.Asp302= | synonymous_variant | 5/11 | ENST00000311895.8 | |
ERCC4 | XM_011522424.4 | c.1044T>C | p.Asp348= | synonymous_variant | 6/12 | ||
ERCC4 | XM_047433774.1 | c.117T>C | p.Asp39= | synonymous_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC4 | ENST00000311895.8 | c.906T>C | p.Asp302= | synonymous_variant | 5/11 | 1 | NM_005236.3 | P1 | |
ENST00000570663.1 | n.250A>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251296Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135830
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GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461026Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 30AN XY: 726890
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 19, 2016 | - - |
Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 31, 2021 | - - |
Xeroderma pigmentosum Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 19, 2022 | - - |
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