rs12187537

Positions:

• chr5-132604212-T-G

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.2524+166T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,218 control chromosomes in the GnomAD database, including 2,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2316 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

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=-0.84).
• BP6: Variant 5-132604212-T-G is Benign according to our data. Variant chr5-132604212-T-G is described in ClinVar as [Benign]. Clinvar id is 1224961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4	c.2524+166T>G		intron_variant		ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.2524+166T>G		intron_variant		1	NM_005732.4	ENSP00000368100	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24589 AN: 152100 Hom.: 2314 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.162 AC: 24587 AN: 152218 Hom.: 2316 Cov.: 32 AF XY: 0.163 AC XY: 12135 AN XY: 74410

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.166

Alfa AF: 0.189 Hom.: 473

Bravo AF: 0.148

Asia WGS AF: 0.181 AC: 633 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.7
DANN	Benign	0.66

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: rs12187537; hg19: chr5-131939904; COSMIC: COSV54749162; COSMIC: COSV54749162;