Genetic Variant NM_005732.4:c.213+790C>T (chr5-132560157-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005732.4(RAD50):c.213+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,946 control chromosomes in the GnomAD database, including 2,426 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 ( 2426 hom., cov: 32)

Consequence

RAD50
NM_005732.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.41

Publications

18 publications found

Variant links:

Genes affected

RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]

RAD50 Gene-Disease associations (from GenCC):

Nijmegen breakage syndrome-like disorder
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RAD50 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4 link	c.213+790C>T		intron_variant	Intron 2 of 24	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 link	c.213+790C>T		intron_variant	Intron 2 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2 link	c.-85+790C>T		intron_variant	Intron 4 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25325

AN:

151828

Hom.:

2424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.167

AC:

25322

AN:

151946

Hom.:

2426

Cov.:

AF XY:

0.168

AC XY:

12498

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.0690

AC:

2861

AN:

41448

American (AMR)

AF:

0.146

AC:

2220

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3472

East Asian (EAS)

AF:

0.177

AC:

917

AN:

5182

South Asian (SAS)

AF:

0.210

AC:

1011

AN:

4822

European-Finnish (FIN)

AF:

0.237

AC:

2492

AN:

10506

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.214

AC:

14535

AN:

67960

Other (OTH)

AF:

0.167

AC:

351

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1062

2124

3186

4248

5310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.178

Hom.:

502

Bravo

AF:

0.152

Asia WGS

AF:

0.178

AC:

621

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.028

(source)

DANN

Benign

0.82

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over