dbSNP rs17783124: RAD51B:c.84+28T>G (chr14-67823655-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133510.4(RAD51B):c.84+28T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,559,548 control chromosomes in the GnomAD database, including 91,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8319 hom., cov: 32)

Exomes 𝑓: 0.34 ( 82826 hom. )

Consequence

RAD51B
NM_133510.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.182

Publications

11 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

RAD51B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 14-67823655-T-G is Benign according to our data. Variant chr14-67823655-T-G is described in ClinVar as Benign. ClinVar VariationId is 1264893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD51B	NM_133510.4	MANE Select	c.84+28T>G	intron	N/A	NP_598194.1	O15315-2
RAD51B	NM_001321821.2		c.84+28T>G	intron	N/A	NP_001308750.1	C9JYJ0
RAD51B	NM_133509.5		c.84+28T>G	intron	N/A	NP_598193.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.84+28T>G	intron	N/A	ENSP00000418859.1	O15315-2
RAD51B	ENST00000487861.5	TSL:1	c.84+28T>G	intron	N/A	ENSP00000419881.1	C9JYJ0
RAD51B	ENST00000487270.5	TSL:1	c.84+28T>G	intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49168

AN:

151950

Hom.:

8298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.0744

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.293

AC:

71103

AN:

242970

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.0743

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.337

AC:

473847

AN:

1407480

Hom.:

82826

Cov.:

AF XY:

0.334

AC XY:

234644

AN XY:

702678

show subpopulations

African (AFR)

AF:

0.344

AC:

11036

AN:

32090

American (AMR)

AF:

0.205

AC:

8802

AN:

42986

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

10187

AN:

25650

East Asian (EAS)

AF:

0.0850

AC:

3338

AN:

39284

South Asian (SAS)

AF:

0.234

AC:

19410

AN:

82826

European-Finnish (FIN)

AF:

0.287

AC:

15206

AN:

53036

Middle Eastern (MID)

AF:

0.350

AC:

1971

AN:

5624

European-Non Finnish (NFE)

AF:

0.360

AC:

384641

AN:

1067438

Other (OTH)

AF:

0.329

AC:

19256

AN:

58546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

14533

29065

43598

58130

72663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12024

24048

36072

48096

60120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.324

AC:

49222

AN:

152068

Hom.:

8319

Cov.:

AF XY:

0.316

AC XY:

23460

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.343

AC:

14236

AN:

41448

American (AMR)

AF:

0.253

AC:

3862

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1430

AN:

3472

East Asian (EAS)

AF:

0.0748

AC:

388

AN:

5188

South Asian (SAS)

AF:

0.239

AC:

1155

AN:

4824

European-Finnish (FIN)

AF:

0.280

AC:

2954

AN:

10558

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24060

AN:

67984

Other (OTH)

AF:

0.326

AC:

688

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1674

3347

5021

6694

8368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.337

Hom.:

2157

Bravo

AF:

0.323

Asia WGS

AF:

0.179

AC:

623

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary breast ovarian cancer syndrome (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.7

(source)

DANN

Benign

0.66

PhyloP100

0.18

PromoterAI

-0.00090

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over