rs2237060

Positions:

• chr5-132635193-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.3390-1922T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,158 control chromosomes in the GnomAD database, including 7,919 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 0.29 (7919 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-1922T>G		intron_variant		ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+2965A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-1922T>G		intron_variant		1	NM_005732.4	ENSP00000368100	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43444 AN: 152040 Hom.: 7926 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.285 AC: 43438 AN: 152158 Hom.: 7919 Cov.: 32 AF XY: 0.278 AC XY: 20704 AN XY: 74386

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.0630

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.293

Alfa AF: 0.395 Hom.: 17156

Bravo AF: 0.277

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.73

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: rs2237060; hg19: chr5-131970885;