rs766164248
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000340611.9(BRAT1):c.2296G>A(p.Asp766Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,609,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D766E) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000340611.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.2296G>A | p.Asp766Asn | missense_variant | 14/14 | ENST00000340611.9 | NP_689956.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.2296G>A | p.Asp766Asn | missense_variant | 14/14 | 1 | NM_152743.4 | ENSP00000339637 | P1 | |
BRAT1 | ENST00000467558.5 | n.4082G>A | non_coding_transcript_exon_variant | 10/10 | 5 | |||||
BRAT1 | ENST00000469750.5 | n.4868G>A | non_coding_transcript_exon_variant | 11/11 | 2 | |||||
BRAT1 | ENST00000493232.5 | n.5002G>A | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152256Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000291 AC: 7AN: 240894Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132040
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1457326Hom.: 0 Cov.: 60 AF XY: 0.00000966 AC XY: 7AN XY: 724664
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152256Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74386
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 03, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 766 of the BRAT1 protein (p.Asp766Asn). This variant is present in population databases (rs766164248, gnomAD 0.02%). This missense change has been observed in individual(s) with epilepsy (Invitae). ClinVar contains an entry for this variant (Variation ID: 577573). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRAT1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at