rs148518198
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_133510.4(RAD51B):c.1036+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000435 in 1,609,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 0 hom. )
Consequence
RAD51B
NM_133510.4 splice_region, intron
NM_133510.4 splice_region, intron
Scores
2
Splicing: ADA: 0.9953
1
1
Clinical Significance
Conservation
PhyloP100: 4.43
Genes affected
RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 14-68468255-G-A is Benign according to our data. Variant chr14-68468255-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 584550.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 66 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD51B | NM_133510.4 | c.1036+5G>A | splice_region_variant, intron_variant | ENST00000471583.6 | NP_598194.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD51B | ENST00000471583.6 | c.1036+5G>A | splice_region_variant, intron_variant | 1 | NM_133510.4 | ENSP00000418859.1 |
Frequencies
GnomAD3 genomes AF: 0.000434 AC: 66AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
66
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000473 AC: 119AN: 251422Hom.: 0 AF XY: 0.000478 AC XY: 65AN XY: 135874
GnomAD3 exomes
AF:
AC:
119
AN:
251422
Hom.:
AF XY:
AC XY:
65
AN XY:
135874
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000435 AC: 634AN: 1457280Hom.: 0 Cov.: 30 AF XY: 0.000427 AC XY: 310AN XY: 725176
GnomAD4 exome
AF:
AC:
634
AN:
1457280
Hom.:
Cov.:
30
AF XY:
AC XY:
310
AN XY:
725176
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000433 AC: 66AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33AN XY: 74490
GnomAD4 genome
AF:
AC:
66
AN:
152304
Hom.:
Cov.:
32
AF XY:
AC XY:
33
AN XY:
74490
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2024 | The c.1036+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 9 in the RAD51B gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneKor MSA | Aug 01, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
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