rs4526098

Positions:

• chr5-132557287-G-A
• chr5-132557287-G-C
• chr5-132557287-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.-38G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,611,840 control chromosomes in the GnomAD database, including 783,609 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 0.93 (66617 hom., cov: 34)
  • Exomes 𝑓: 0.99 (716992 hom.)
• Consequence: RAD50 NM_005732.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.-38G>A		5_prime_UTR_variant	1/25	ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.-38G>A		5_prime_UTR_variant	1/25	1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141497 AN: 152178 Hom.: 66576 Cov.: 34

Gnomad AFR AF: 0.762

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.948

GnomAD3 exomes AF: 0.979 AC: 246201 AN: 251458 Hom.: 120992 AF XY: 0.984 AC XY: 133709 AN XY: 135906

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.992

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.990 AC: 1445590 AN: 1459544 Hom.: 716992 Cov.: 46 AF XY: 0.991 AC XY: 719847 AN XY: 726220

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.983

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.992

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.981

GnomAD4 genome AF: 0.930 AC: 141591 AN: 152296 Hom.: 66617 Cov.: 34 AF XY: 0.932 AC XY: 69401 AN XY: 74470

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.948

Alfa AF: 0.968 Hom.: 28682

Bravo AF: 0.918

Asia WGS AF: 0.979 AC: 3404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs4526098; hg19: chr5-131892979; COSMIC: COSV99528532; COSMIC: COSV99528532;