NM_133510.4:c.853+896T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133510.4(RAD51B):​c.853+896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00996 in 152,294 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 31 hom., cov: 32)

Consequence

RAD51B
NM_133510.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

2 publications found
Variant links:
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]
RAD51B Gene-Disease associations (from GenCC):
  • primary ovarian failure
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD51BNM_133510.4 linkc.853+896T>C intron_variant Intron 8 of 10 ENST00000471583.6 NP_598194.1 O15315-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD51BENST00000471583.6 linkc.853+896T>C intron_variant Intron 8 of 10 1 NM_133510.4 ENSP00000418859.1 O15315-2

Frequencies

GnomAD3 genomes
AF:
0.00992
AC:
1510
AN:
152176
Hom.:
31
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0231
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0112
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0579
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.00254
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00909
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00996
AC:
1517
AN:
152294
Hom.:
31
Cov.:
32
AF XY:
0.0104
AC XY:
773
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.0231
AC:
961
AN:
41554
American (AMR)
AF:
0.0114
AC:
175
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.0578
AC:
300
AN:
5188
South Asian (SAS)
AF:
0.00311
AC:
15
AN:
4828
European-Finnish (FIN)
AF:
0.00254
AC:
27
AN:
10618
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000265
AC:
18
AN:
68024
Other (OTH)
AF:
0.00900
AC:
19
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
73
146
220
293
366
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00651
Hom.:
1
Bravo
AF:
0.0118
Asia WGS
AF:
0.0240
AC:
84
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.11
DANN
Benign
0.27
PhyloP100
-1.8
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12432392; hg19: chr14-68759593; API