rs2074369

chr5-132637971-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.3476-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,229,542 control chromosomes in the GnomAD database, including 39,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (10444 hom., cov: 32)
  • Exomes 𝑓: 0.22 (28922 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.327

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]

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 5-132637971-T-C is Benign according to our data. Variant chr5-132637971-T-C is described in ClinVar as [Benign]. Clinvar id is 1180917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.3476-110T>C		intron_variant		ENST00000378823.8
TH2LCRR	NR_132124.1	n.153+187A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.3476-110T>C		intron_variant		1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49490 AN: 151962 Hom.: 10405 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.220 AC: 237494 AN: 1077462 Hom.: 28922 AF XY: 0.222 AC XY: 121883 AN XY: 550256

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.326 AC: 49577 AN: 152080 Hom.: 10444 Cov.: 32 AF XY: 0.323 AC XY: 24041 AN XY: 74346

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.282

Alfa AF: 0.298 Hom.: 2109

Bravo AF: 0.335

Asia WGS AF: 0.230 AC: 803 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	-0.96
Cadd	Benign	5.6
Dann	Benign	0.82

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: rs2074369; hg19: chr5-131973663; COSMIC: COSV54756994; COSMIC: COSV54756994;