NM_005732.4:c.3390-7628G>A

Variant names:

• chr5-132629487-G-A
• rs3798134
• NM_005732.4:c.3390-7628G>A

Variant summary

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

The NM_005732.4(RAD50):​c.3390-7628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,034 control chromosomes in the GnomAD database, including 5,770 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 0.26 (5770 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 22 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3390-7628G>A		intron_variant	Intron 21 of 24	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3390-7628G>A		intron_variant	Intron 21 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3093-7628G>A		intron_variant	Intron 23 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39688 AN: 151916 Hom.: 5747 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.261 AC: 39755 AN: 152034 Hom.: 5770 Cov.: 31 AF XY: 0.261 AC XY: 19402 AN XY: 74320

African (AFR) AF: 0.389 AC: 16112 AN: 41422

American (AMR) AF: 0.180 AC: 2750 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.177 AC: 914 AN: 5178

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4818

European-Finnish (FIN) AF: 0.244 AC: 2575 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14765 AN: 67990

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.228 Hom.: 16161

Bravo AF: 0.260

Asia WGS AF: 0.210 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.60
PhyloP100		1.3
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: rs3798134; hg19: chr5-131965179;