chr5-132560157-C-T

Variant names:

• chr5-132560157-C-T
• rs2706338
• NM_005732.4:c.213+790C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 18 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	NM_005732.4	MANE Select	c.213+790C>T		intron	N/A	NP_005723.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.213+790C>T		intron	N/A	ENSP00000368100.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-85+790C>T		intron	N/A	ENSP00000492349.2
	RAD50	ENST00000416135.5	TSL:1	c.-85+790C>T		intron	N/A	ENSP00000389515.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25325 AN: 151828 Hom.: 2424 Cov.: 32

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.: 32 AF XY: 0.168 AC XY: 12498 AN XY: 74252

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: 57 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14535 AN: 67960

Other (OTH) AF: 0.167 AC: 351 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.028
DANN	Benign	0.82
PhyloP100		-2.4
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: rs2706338; hg19: chr5-131895849;