rs2040704

Positions:

• chr5-132637485-A-G
• chr5-132637485-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005732.4(RAD50):​c.3475+285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,758 control chromosomes in the GnomAD database, including 10,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (10548 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-132637485-A-G is Benign according to our data. Variant chr5-132637485-A-G is described in ClinVar as [Benign]. Clinvar id is 1282436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4	c.3475+285A>G		intron_variant		ENST00000378823.8	NP_005723.2
TH2LCRR	NR_132124.1	n.153+673T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.3475+285A>G		intron_variant		1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000640655.2	c.3178+285A>G		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49601 AN: 151642 Hom.: 10505 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.327 AC: 49692 AN: 151758 Hom.: 10548 Cov.: 31 AF XY: 0.325 AC XY: 24076 AN XY: 74178

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.284

Alfa AF: 0.230 Hom.: 5371

Bravo AF: 0.337

Asia WGS AF: 0.232 AC: 810 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.4
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs2040704; hg19: chr5-131973177;