NM_005732.4:c.3390-7698C>T

Variant names:

• chr5-132629417-C-T
• rs3798135
• NM_005732.4:c.3390-7698C>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.3390-7698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,922 control chromosomes in the GnomAD database, including 5,794 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 0.26 (5794 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 23 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-7698C>T		intron_variant	Intron 21 of 24	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-7698C>T		intron_variant	Intron 21 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3093-7698C>T		intron_variant	Intron 23 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39739 AN: 151804 Hom.: 5771 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.262 AC: 39806 AN: 151922 Hom.: 5794 Cov.: 31 AF XY: 0.262 AC XY: 19426 AN XY: 74260

African (AFR) AF: 0.390 AC: 16151 AN: 41408

American (AMR) AF: 0.181 AC: 2760 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3468

East Asian (EAS) AF: 0.178 AC: 920 AN: 5168

South Asian (SAS) AF: 0.234 AC: 1124 AN: 4810

European-Finnish (FIN) AF: 0.244 AC: 2575 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14755 AN: 67936

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.270 Hom.: 1151

Bravo AF: 0.260

Asia WGS AF: 0.212 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.43
PhyloP100		-1.6
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: rs3798135; hg19: chr5-131965109;