rs376179903
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_152743.4(BRAT1):c.924-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,555,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152743.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.924-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.924-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000977 AC: 16AN: 163728Hom.: 0 AF XY: 0.0000808 AC XY: 7AN XY: 86670
GnomAD4 exome AF: 0.0000499 AC: 70AN: 1403690Hom.: 0 Cov.: 31 AF XY: 0.0000476 AC XY: 33AN XY: 693048
GnomAD4 genome ? AF: 0.000617 AC: 94AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2021 | Has not been previously published as pathogenic or benign to our knowledge In silico analysis supports a deleterious effect on splicing Observed in 0.0185% (36/195066 alleles) in large population cohorts (Lek et al., 2016) - |
Neonatal-onset encephalopathy with rigidity and seizures Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at