rs11955168

chr5-132621215-C-T

Variant summary

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

The NM_005732.4(RAD50):c.3389+2921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 152,164 control chromosomes in the GnomAD database, including 407 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 0.038 (407 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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 (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.3389+2921C>T		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.3389+2921C>T		intron_variant		1	NM_005732.4	P1
RAD50	ENST00000533482.5	c.*3015+2921C>T		intron_variant, NMD_transcript_variant		1
RAD50	ENST00000455677.1	c.24+2921C>T		intron_variant		5
RAD50	ENST00000651249.1	c.225+2921C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5854 AN: 152046 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0384 AC: 5844 AN: 152164 Hom.: 407 Cov.: 32 AF XY: 0.0431 AC XY: 3210 AN XY: 74412

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.0776

Gnomad4 FIN AF: 0.0479

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0379 Hom.: 122

Bravo AF: 0.0422

Asia WGS AF: 0.184 AC: 640 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	1.6
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11955168; hg19: chr5-131956907;