chr14-68221985-C-T

Variant summary

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

The NM_133510.4(RAD51B):​c.757-69899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,068 control chromosomes in the GnomAD database, including 2,482 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 0.17 ( 2482 hom., cov: 32)

Consequence

RAD51B
NM_133510.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.972

Publications

0 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=-1.0).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD51BNM_133510.4 linkc.757-69899C>T intron_variant Intron 7 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.757-69899C>T intron_variant Intron 7 of 10 1 NM_133510.4 ENSP00000418859.1 O15315-2

Frequencies

GnomAD3 genomes
AF:
0.175
AC:
26557
AN:
151950
Hom.:
2473
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.221
Gnomad AMI
AF:
0.135
Gnomad AMR
AF:
0.171
Gnomad ASJ
AF:
0.287
Gnomad EAS
AF:
0.0227
Gnomad SAS
AF:
0.169
Gnomad FIN
AF:
0.126
Gnomad MID
AF:
0.348
Gnomad NFE
AF:
0.160
Gnomad OTH
AF:
0.207
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.175
AC:
26596
AN:
152068
Hom.:
2482
Cov.:
32
AF XY:
0.173
AC XY:
12846
AN XY:
74328
show subpopulations
African (AFR)
AF:
0.221
AC:
9167
AN:
41482
American (AMR)
AF:
0.171
AC:
2615
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.287
AC:
996
AN:
3472
East Asian (EAS)
AF:
0.0226
AC:
117
AN:
5180
South Asian (SAS)
AF:
0.169
AC:
815
AN:
4824
European-Finnish (FIN)
AF:
0.126
AC:
1328
AN:
10568
Middle Eastern (MID)
AF:
0.361
AC:
106
AN:
294
European-Non Finnish (NFE)
AF:
0.160
AC:
10898
AN:
67954
Other (OTH)
AF:
0.204
AC:
431
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1144
2288
3433
4577
5721
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
278
556
834
1112
1390
<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:
0.164
Hom.:
277
Bravo
AF:
0.181
Asia WGS
AF:
0.125
AC:
435
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.0
DANN
Benign
0.60
PhyloP100
-0.97
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: rs1631742; hg19: chr14-68688702; API