5-132636210-C-T

Variant names:

• chr5-132636210-C-T
• rs12653750
• NM_005732.4:c.3390-905C>T

Variant summary

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

The NM_005732.4(RAD50):​c.3390-905C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,088 control chromosomes in the GnomAD database, including 2,657 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 0.18 (2657 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 19 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-905C>T		intron_variant	Intron 21 of 24	ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+1948G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-905C>T		intron_variant	Intron 21 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3093-905C>T		intron_variant	Intron 23 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26996 AN: 151970 Hom.: 2654 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.178 AC: 27001 AN: 152088 Hom.: 2657 Cov.: 32 AF XY: 0.179 AC XY: 13342 AN XY: 74334

African (AFR) AF: 0.101 AC: 4190 AN: 41502

American (AMR) AF: 0.148 AC: 2264 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 762 AN: 3472

East Asian (EAS) AF: 0.176 AC: 909 AN: 5170

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2564 AN: 10534

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14619 AN: 67990

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.191 Hom.: 1253

Bravo AF: 0.163

Asia WGS AF: 0.191 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-1.9
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: rs12653750; hg19: chr5-131971902;