rs775426160
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_005732.4(RAD50):c.3753-4G>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 0.00000682 in 1,612,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 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.3753-4G>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000378823.8 | |||
TH2LCRR | NR_132125.1 | n.189+24C>A | intron_variant, non_coding_transcript_variant | ||||
TH2LCRR | NR_132126.1 | n.175-3909C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.3753-4G>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005732.4 | P1 | |||
TH2LCRR | ENST00000435042.1 | n.194+9C>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251222Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135786
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460434Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726664
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 07, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2018 | The c.3753-4G>T intronic variant results from a G to T substitution 4 nucleotides upstream from coding exon 25 in the RAD50 gene. This nucleotide position is poorly conserved, and T is the reference nucleotide in the majority of available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 11, 2022 | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00011 (4/35434 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect RAD50 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at