rs2299014

chr5-132567707-A-Cchr5-132567707-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):c.214-8070A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,074 control chromosomes in the GnomAD database, including 9,362 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 0.31 (9362 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.214-8070A>C		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.214-8070A>C		intron_variant		1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47366 AN: 151956 Hom.: 9364 Cov.: 31

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.311 AC: 47363 AN: 152074 Hom.: 9362 Cov.: 31 AF XY: 0.306 AC XY: 22760 AN XY: 74338

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.0650

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.309

Alfa AF: 0.322 Hom.: 1374

Bravo AF: 0.295

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs2299014; hg19: chr5-131903399;