5-132641857-T-G

Variant names:

• chr5-132641857-T-G
• rs2214370
• NM_005732.4:c.3753-321T>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.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
• Publications: 3 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	NM_005732.4	MANE Select	c.3753-321T>G		intron	N/A	NP_005723.2
	TH2LCRR	NR_132125.1		n.189+341A>C		intron	N/A
	TH2LCRR	NR_132126.1		n.175-3592A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.3753-321T>G		intron	N/A	ENSP00000368100.4	Q92878-1
	ENSG00000283782	ENST00000638452.2	TSL:5	c.3456-321T>G		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	TH2LCRR	ENST00000458509.1	TSL:1	n.189+341A>C		intron	N/A

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

African (AFR) AF: 0.285 AC: 1466 AN: 5136

American (AMR) AF: 0.0281 AC: 174 AN: 6192

Ashkenazi Jewish (ASJ) AF: 0.00120 AC: 6 AN: 4986

East Asian (EAS) AF: 0.0000999 AC: 1 AN: 10008

South Asian (SAS) AF: 0.00927 AC: 106 AN: 11438

European-Finnish (FIN) AF: 0.000164 AC: 1 AN: 6110

Middle Eastern (MID) AF: 0.0335 AC: 23 AN: 686

European-Non Finnish (NFE) AF: 0.00373 AC: 340 AN: 91054

Other (OTH) AF: 0.0228 AC: 206 AN: 9044

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

African (AFR) AF: 0.293 AC: 12159 AN: 41516

American (AMR) AF: 0.0348 AC: 532 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00412 AC: 280 AN: 68026

Other (OTH) AF: 0.0582 AC: 123 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		0.22
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: rs2214370; hg19: chr5-131977549;