chr5-132580071-CT-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_005732.4(RAD50):c.756+7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000331 in 1,602,076 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005732.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.756+6delT | splice_region_variant, intron_variant | Intron 5 of 24 | 1 | NM_005732.4 | ENSP00000368100.4 | |||
ENSG00000283782 | ENST00000640655.2 | c.459+6delT | splice_region_variant, intron_variant | Intron 6 of 25 | 5 | ENSP00000491596.2 |
Frequencies
GnomAD3 genomes AF: 0.00170 AC: 258AN: 152116Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000420 AC: 105AN: 249798Hom.: 3 AF XY: 0.000251 AC XY: 34AN XY: 135314
GnomAD4 exome AF: 0.000186 AC: 270AN: 1449842Hom.: 5 Cov.: 30 AF XY: 0.000168 AC XY: 121AN XY: 722146
GnomAD4 genome AF: 0.00171 AC: 260AN: 152234Hom.: 2 Cov.: 32 AF XY: 0.00173 AC XY: 129AN XY: 74416
ClinVar
Submissions by phenotype
not specified Benign:3
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Variant summary: The RAD50 c.756+7delT variant involves the alteration of a non-conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 157/276094 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.006342 (152/23968). This frequency is about 101 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -
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Hereditary cancer-predisposing syndrome Benign:2
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The variant is found in BR-OV-HEREDIC panel(s). -
not provided Benign:1
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Nijmegen breakage syndrome-like disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at