chr7-2538101-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152743.4(BRAT1):āc.2434T>Cā(p.Phe812Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,584,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_152743.4 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.2434T>C | p.Phe812Leu | 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.2434T>C | p.Phe812Leu | missense_variant | 14/14 | 1 | NM_152743.4 | ENSP00000339637 | P1 | |
BRAT1 | ENST00000467558.5 | n.4220T>C | non_coding_transcript_exon_variant | 10/10 | 5 | |||||
BRAT1 | ENST00000469750.5 | n.5006T>C | non_coding_transcript_exon_variant | 11/11 | 2 | |||||
BRAT1 | ENST00000493232.5 | n.5140T>C | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000300 AC: 7AN: 233290Hom.: 0 AF XY: 0.0000469 AC XY: 6AN XY: 127960
GnomAD4 exome AF: 0.0000300 AC: 43AN: 1432760Hom.: 0 Cov.: 31 AF XY: 0.0000339 AC XY: 24AN XY: 707770
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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 | Jul 15, 2018 | This sequence change replaces phenylalanine with leucine at codon 812 of the BRAT1 protein (p.Phe812Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs757188244, ExAC 0.005%). This variant has not been reported in the literature in individuals with BRAT1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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