chr1-226380094-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001618.4(PARP1):c.1371C>T(p.Asp457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,072 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 (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
PARP1
NM_001618.4 synonymous
NM_001618.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.96
Genes affected
PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 1-226380094-G-A is Benign according to our data. Variant chr1-226380094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3057382.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.96 with no splicing effect.
BS2
?
High AC in GnomAd at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARP1 | NM_001618.4 | c.1371C>T | p.Asp457= | synonymous_variant | 10/23 | ENST00000366794.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARP1 | ENST00000366794.10 | c.1371C>T | p.Asp457= | synonymous_variant | 10/23 | 1 | NM_001618.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000175 AC: 44AN: 251328Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135860
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GnomAD4 exome AF: 0.000263 AC: 384AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.000252 AC XY: 183AN XY: 727228
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PARP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 18, 2019 | This variant is classified as likely 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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Name
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BayesDel_noAF
Benign
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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