rs17166050

Positions:

chr5-132579521-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005732.4(RAD50):c.551+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,597,502 control chromosomes in the GnomAD database, including 31,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2701 hom., cov: 32)

Exomes 𝑓: 0.20 ( 28912 hom. )

Consequence

RAD50
NM_005732.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.192

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-132579521-G-A is Benign according to our data. Variant chr5-132579521-G-A is described in ClinVar as [Benign]. Clinvar id is 259870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-132579521-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4 linkuse as main transcript	c.551+19G>A		intron_variant		ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 linkuse as main transcript	c.551+19G>A		intron_variant		1	NM_005732.4	ENSP00000368100	P1	Q92878-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27552

AN:

151980

Hom.:

2697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.197

AC:

49412

AN:

250610

Hom.:

5184

AF XY:

0.202

AC XY:

27455

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.197

AC:

284038

AN:

1445404

Hom.:

28912

Cov.:

AF XY:

0.199

AC XY:

143156

AN XY:

719884

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.181

AC:

27559

AN:

152098

Hom.:

2701

Cov.:

AF XY:

0.183

AC XY:

13623

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.210

Hom.:

779

Bravo

AF:

0.168

Asia WGS

AF:

0.188

AC:

656

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 24093751) -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 24, 2016	Variant summary: The RAD50 c.551+19G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant along with 4/5 splice site tools predicting the variant not to have an impact on splicing. This variant was found in 24021/120846 control chromosomes (2524 homozygotes) at a frequency of 0.1987736, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this variant is a common benign polymorphism. Taken together, this variant is classified as Benign. -

Nijmegen breakage syndrome-like disorder

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Familial cancer of breast

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

DANN

Benign

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over