3-9734400-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001003694.2(BRPF1):c.260G>A(p.Arg87His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,064 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 Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
BRPF1
NM_001003694.2 missense
NM_001003694.2 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.77
Genes affected
BRPF1 (HGNC:14255): (bromodomain and PHD finger containing 1) This gene encodes a bromodomain, PHD finger and chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain containing protein. The encoded protein is a component of the MOZ/MORF histone acetyltransferase complexes which function as a transcriptional regulators. This protein binds to the catalytic MYST domains of the MOZ and MORF proteins and may play a role in stimulating acetyltransferase and transcriptional activity of the complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BRPF1. . Gene score misZ 3.8305 (greater than the threshold 3.09). Trascript score misZ 4.9876 (greater than threshold 3.09). GenCC has associacion of gene with intellectual developmental disorder with dysmorphic facies and ptosis.
BP4
Computational evidence support a benign effect (MetaRNN=0.32954073).
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRPF1 | NM_001003694.2 | c.260G>A | p.Arg87His | missense_variant | 2/14 | ENST00000383829.7 | NP_001003694.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRPF1 | ENST00000383829.7 | c.260G>A | p.Arg87His | missense_variant | 2/14 | 1 | NM_001003694.2 | ENSP00000373340 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251084Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135746
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74402
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare | May 20, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
P;B;B;.;.;B
Vest4
MutPred
Loss of MoRF binding (P = 0.0311);Loss of MoRF binding (P = 0.0311);Loss of MoRF binding (P = 0.0311);Loss of MoRF binding (P = 0.0311);Loss of MoRF binding (P = 0.0311);Loss of MoRF binding (P = 0.0311);
MVP
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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