rs864622704
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_005732.4(RAD50):c.3752+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
RAD50
NM_005732.4 splice_donor_region, intron
NM_005732.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.03273
2
Clinical Significance
Conservation
PhyloP100: 0.0610
Genes affected
RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 5-132640808-A-G is Benign according to our data. Variant chr5-132640808-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 220951.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.3752+3A>G | splice_donor_region_variant, intron_variant | ENST00000378823.8 | |||
TH2LCRR | NR_132124.1 | n.45+938T>C | intron_variant, non_coding_transcript_variant | ||||
TH2LCRR | NR_132125.1 | n.189+1390T>C | intron_variant, non_coding_transcript_variant | ||||
TH2LCRR | NR_132126.1 | n.175-2543T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.3752+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_005732.4 | P1 | |||
TH2LCRR | ENST00000435042.1 | n.282+938T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135876
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461054Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726840
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74228
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2020 | The c.3752+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 24 in the RAD50 gene. This nucleotide position is not adequately covered in vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at