1-226380111-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001618.4(PARP1):c.1354C>A(p.Arg452=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,614,066 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 0.00038 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
PARP1
NM_001618.4 synonymous
NM_001618.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 7.50
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
Variant 1-226380111-G-T is Benign according to our data. Variant chr1-226380111-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3208665.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 58 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARP1 | NM_001618.4 | c.1354C>A | p.Arg452= | synonymous_variant | 10/23 | ENST00000366794.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARP1 | ENST00000366794.10 | c.1354C>A | p.Arg452= | synonymous_variant | 10/23 | 1 | NM_001618.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000259 AC: 65AN: 251354Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135882
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GnomAD4 exome AF: 0.000296 AC: 433AN: 1461772Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 205AN XY: 727202
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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