Variant rs4526098 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26

Variant links:

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]

RAD50 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
RAD50	NM_005732.4 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/25	ENST00000378823.8	NP_005723.2	Q92878-1A5D6Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/25	1	NM_005732.4	ENSP00000368100.4		Q92878-1
ENSG00000283782	ENST00000640655.2 linkuse as main transcript	c.-168-1997G>A		intron_variant		5		ENSP00000491596.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.930

AC:

141497

AN:

152178

Hom.:

66576

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.991

AC XY:

719847

AN XY:

726220

show subpopulations

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.:

AF XY:

0.932

AC XY:

69401

AN XY:

74470

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over