chr5-132637971-T-C

Variant names:

• chr5-132637971-T-C
• rs2074369
• NM_005732.4:c.3476-110T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005732.4(RAD50):​c.3476-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,229,542 control chromosomes in the GnomAD database, including 39,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (10444 hom., cov: 32)
  • Exomes 𝑓: 0.22 (28922 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.327
• Publications: 21 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 5-132637971-T-C is Benign according to our data. Variant chr5-132637971-T-C is described in ClinVar as Benign. ClinVar VariationId is 1180917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3476-110T>C		intron_variant	Intron 22 of 24	ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+187A>G		intron_variant	Intron 2 of 2
TH2LCRR	NR_132125.1	n.*77A>G		downstream_gene_variant
TH2LCRR	NR_132126.1	n.*77A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3476-110T>C		intron_variant	Intron 22 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.3179-110T>C		intron_variant	Intron 24 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49490 AN: 151962 Hom.: 10405 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.220 AC: 237494 AN: 1077462 Hom.: 28922 AF XY: 0.222 AC XY: 121883 AN XY: 550256

African (AFR) AF: 0.613 AC: 15466 AN: 25248

American (AMR) AF: 0.184 AC: 7193 AN: 39198

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5325 AN: 22938

East Asian (EAS) AF: 0.198 AC: 7254 AN: 36694

South Asian (SAS) AF: 0.245 AC: 18246 AN: 74362

European-Finnish (FIN) AF: 0.253 AC: 12440 AN: 49096

Middle Eastern (MID) AF: 0.270 AC: 952 AN: 3522

European-Non Finnish (NFE) AF: 0.205 AC: 159749 AN: 779038

Other (OTH) AF: 0.229 AC: 10869 AN: 47366

GnomAD4 genome AF: 0.326 AC: 49577 AN: 152080 Hom.: 10444 Cov.: 32 AF XY: 0.323 AC XY: 24041 AN XY: 74346

African (AFR) AF: 0.607 AC: 25177 AN: 41462

American (AMR) AF: 0.207 AC: 3157 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3468

East Asian (EAS) AF: 0.178 AC: 925 AN: 5186

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4822

European-Finnish (FIN) AF: 0.244 AC: 2579 AN: 10576

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14968 AN: 67978

Other (OTH) AF: 0.282 AC: 593 AN: 2106

Alfa AF: 0.288 Hom.: 3051

Bravo AF: 0.335

Asia WGS AF: 0.230 AC: 803 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.6
DANN	Benign	0.82
PhyloP100		-0.33
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: rs2074369; hg19: chr5-131973663; COSMIC: COSV54756994; COSMIC: COSV54756994;