NM_005732.4:c.3037-3169T>A

Variant names:

• chr5-132612834-T-A
• rs2245460
• NM_005732.4:c.3037-3169T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.3037-3169T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,142 control chromosomes in the GnomAD database, including 6,866 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 0.28 (6866 hom., cov: 30)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 7 publications found

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

ENSG00000283782 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	NM_005732.4	MANE Select	c.3037-3169T>A		intron	N/A	NP_005723.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.3037-3169T>A		intron	N/A	ENSP00000368100.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.2740-3169T>A		intron	N/A	ENSP00000492349.2
	RAD50	ENST00000533482.5	TSL:1	n.*2663-3169T>A		intron	N/A	ENSP00000431225.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42322 AN: 151030 Hom.: 6844 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.280 AC: 42386 AN: 151142 Hom.: 6866 Cov.: 30 AF XY: 0.280 AC XY: 20636 AN XY: 73824

African (AFR) AF: 0.461 AC: 19017 AN: 41218

American (AMR) AF: 0.191 AC: 2890 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3464

East Asian (EAS) AF: 0.176 AC: 906 AN: 5150

South Asian (SAS) AF: 0.237 AC: 1134 AN: 4780

European-Finnish (FIN) AF: 0.232 AC: 2414 AN: 10388

Middle Eastern (MID) AF: 0.253 AC: 73 AN: 288

European-Non Finnish (NFE) AF: 0.214 AC: 14490 AN: 67710

Other (OTH) AF: 0.253 AC: 530 AN: 2096

Alfa AF: 0.159 Hom.: 316

Bravo AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.19
PhyloP100		0.077
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

Other links and lift over

dbSNP: rs2245460; hg19: chr5-131948526;