rs778261497
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_005732.4(RAD50):c.1052-5A>T 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 0.0000274 in 1,603,386 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_005732.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.1052-5A>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.1052-5A>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151854Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000332 AC: 8AN: 240650Hom.: 0 AF XY: 0.0000307 AC XY: 4AN XY: 130294
GnomAD4 exome AF: 0.0000296 AC: 43AN: 1451532Hom.: 0 Cov.: 32 AF XY: 0.0000305 AC XY: 22AN XY: 721822
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151854Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74140
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 02, 2023 | The c.1052-5A>T intronic variant results from an A to T substitution 5 nucleotides upstream from coding exon 8 in the RAD50 gene. This nucleotide position is poorly conserved in available vertebrate species. RNA studies have demonstrated that this alteration does not result in abnormal splicing in the set of samples tested (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at