rs150245975
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001429.4(EP300):āc.316A>Gā(p.Ser106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001429.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.316A>G | p.Ser106Gly | missense_variant | 2/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.316A>G | p.Ser106Gly | missense_variant | 2/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.316A>G | p.Ser106Gly | missense_variant | 2/31 | 1 | NM_001429.4 | P2 | |
EP300 | ENST00000674155.1 | c.316A>G | p.Ser106Gly | missense_variant | 2/30 | A2 | |||
EP300 | ENST00000703544.1 | c.316A>G | p.Ser106Gly | missense_variant, NMD_transcript_variant | 2/30 | ||||
EP300 | ENST00000703545.1 | c.202A>G | p.Ser68Gly | missense_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes ? AF: 0.000512 AC: 78AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000481 AC: 121AN: 251456Hom.: 0 AF XY: 0.000515 AC XY: 70AN XY: 135904
GnomAD4 exome AF: 0.000765 AC: 1118AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.000743 AC XY: 540AN XY: 727232
GnomAD4 genome ? AF: 0.000512 AC: 78AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33AN XY: 74492
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The EP300 p.Ser106Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs150245975) and ClinVar (classified as likely benign by Illumina for Rubinstein-Taybi Syndrome). The variant was identified in control databases in 136 of 282856 chromosomes at a frequency of 0.000481 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 129 of 129168 chromosomes (freq: 0.000999), African in 5 of 24964 chromosomes (freq: 0.0002), Other in 1 of 7224 chromosomes (freq: 0.000138) and Latino in 1 of 35440 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) or South Asian populations. The p.Ser106 residue is conserved in mammals but not in more distantly related organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | EP300: BP4, BS1 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2019 | - - |
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
EP300-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 14, 2022 | 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). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at