5-132641857-T-G

Variant summary

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

The NM_005732.4(RAD50):c.3753-321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 296,930 control chromosomes in the GnomAD database, including 2,063 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 0.087 (1815 hom., cov: 32)
  • Exomes 𝑓: 0.016 (248 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.3753-321T>G		intron_variant		ENST00000378823.8
TH2LCRR	NR_132125.1	n.189+341A>C		intron_variant, non_coding_transcript_variant
TH2LCRR	NR_132126.1	n.175-3592A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.3753-321T>G		intron_variant		1	NM_005732.4	P1
TH2LCRR	ENST00000435042.1	n.195-24A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13130 AN: 152158 Hom.: 1803 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.0161 AC: 2323 AN: 144654 Hom.: 248 Cov.: 0 AF XY: 0.0147 AC XY: 1085 AN XY: 73908

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.00120

Gnomad4 EAS exome AF: 0.0000999

Gnomad4 SAS exome AF: 0.00927

Gnomad4 FIN exome AF: 0.000164

Gnomad4 NFE exome AF: 0.00373

Gnomad4 OTH exome AF: 0.0228

GnomAD4 genome AF: 0.0865 AC: 13177 AN: 152276 Hom.: 1815 Cov.: 32 AF XY: 0.0835 AC XY: 6219 AN XY: 74482

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00412

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0121 Hom.: 24

Bravo AF: 0.0998

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.6
Dann	Benign	0.77

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: rs2214370; hg19: chr5-131977549;