rs2301713

chr5-132616304-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005732.4(RAD50):c.3164+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,120 control chromosomes in the GnomAD database, including 4,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4196 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.989

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-132616304-T-C is Benign according to our data. Variant chr5-132616304-T-C is described in ClinVar as [Benign]. Clinvar id is 1182998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.3164+174T>C		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.3164+174T>C		intron_variant		1	NM_005732.4	P1
RAD50	ENST00000533482.5	c.*2790+174T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34931 AN: 152002 Hom.: 4192 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.230 AC: 34949 AN: 152120 Hom.: 4196 Cov.: 32 AF XY: 0.231 AC XY: 17163 AN XY: 74374

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.213

Alfa AF: 0.213 Hom.: 3537

Bravo AF: 0.223

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.6
Dann	Benign	0.58

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: rs2301713; hg19: chr5-131951996;