chr22-41158483-T-C
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001429.4(EP300):āc.3573T>Cā(p.Tyr1191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,152 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 ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000018 ( 0 hom. )
Consequence
EP300
NM_001429.4 synonymous
NM_001429.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.371
Genes affected
EP300 (HGNC:3373): (E1A binding protein p300) This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [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=-0.56).
BP6
Variant 22-41158483-T-C is Benign according to our data. Variant chr22-41158483-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1555273.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.371 with no splicing effect.
BS2
High AC in GnomAdExome4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.3573T>C | p.Tyr1191= | synonymous_variant | 19/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.3495T>C | p.Tyr1165= | synonymous_variant | 18/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.3573T>C | p.Tyr1191= | synonymous_variant | 19/31 | 1 | NM_001429.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152258Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251288Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135832
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727194
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152376Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74520
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2023 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at