5-132636566-C-G

Variant names:

• chr5-132636566-C-G
• rs2040703
• NM_005732.4:c.3390-549C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.3390-549C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,018 control chromosomes in the GnomAD database, including 10,893 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 0.33 (10893 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 10 publications found

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]

ENSG00000283782 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-549C>G		intron_variant	Intron 21 of 24	ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+1592G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-549C>G		intron_variant	Intron 21 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3093-549C>G		intron_variant	Intron 23 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50280 AN: 151900 Hom.: 10852 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.331 AC: 50368 AN: 152018 Hom.: 10893 Cov.: 32 AF XY: 0.329 AC XY: 24426 AN XY: 74292

African (AFR) AF: 0.624 AC: 25853 AN: 41448

American (AMR) AF: 0.209 AC: 3185 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3466

East Asian (EAS) AF: 0.178 AC: 923 AN: 5178

South Asian (SAS) AF: 0.246 AC: 1185 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2583 AN: 10564

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14986 AN: 67964

Other (OTH) AF: 0.285 AC: 601 AN: 2108

Alfa AF: 0.292 Hom.: 953

Bravo AF: 0.341

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.37
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2040703; hg19: chr5-131972258;