chr5-132642271-T-C

Position:

chr5-132642271-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005732.4(RAD50):c.3846T>C(p.Tyr1282Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00948 in 1,613,976 control chromosomes in the GnomAD database, including 1,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 569 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 559 hom. )

Consequence

RAD50
NM_005732.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0570

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 5-132642271-T-C is Benign according to our data. Variant chr5-132642271-T-C is described in ClinVar as [Benign]. Clinvar id is 183705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.057 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 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.3846T>C	p.Tyr1282Tyr	synonymous_variant	25/25	ENST00000378823.8	NP_005723.2	Q92878-1A5D6Y3
TH2LCRR	NR_132125.1 linkuse as main transcript	n.116A>G		non_coding_transcript_exon_variant	2/3
TH2LCRR	NR_132126.1 linkuse as main transcript	n.175-4006A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 linkuse as main transcript	c.3846T>C	p.Tyr1282Tyr	synonymous_variant	25/25	1	NM_005732.4	ENSP00000368100.4		Q92878-1
ENSG00000283782	ENST00000640655.2 linkuse as main transcript	c.3549T>C	p.Tyr1183Tyr	synonymous_variant	26/26	5		ENSP00000491596.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7251

AN:

152162

Hom.:

569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.0267

GnomAD3 exomes

AF:

0.0124

AC:

3124

AN:

251316

Hom.:

240

AF XY:

0.00939

AC XY:

1275

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.00795

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000731

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00550

AC:

8033

AN:

1461696

Hom.:

559

Cov.:

AF XY:

0.00494

AC XY:

3594

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.00854

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.00980

GnomAD4 genome

AF:

0.0477

AC:

7262

AN:

152280

Hom.:

569

Cov.:

AF XY:

0.0467

AC XY:

3480

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0542

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 24, 2016	Variant summary: The RAD50 c.3846T>C (p.Tyr1282Tyr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool (MutationTaster) predicts a polymorphism outcome for this variant. This variant was found in 1833/121336 control chromosomes (146 homozygotes) at a frequency of 0.0151068, which is approximately 242 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this variant is likely a benign polymorphism. It is a common polymorphism in African population with allele frequency of 16.52% (1717/10392 chromosomes) including 145 homozygotes. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 19, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Quest Diagnostics Nichols Institute San Juan Capistrano

Mar 16, 2021

- -

Familial cancer of breast

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Nijmegen breakage syndrome-like disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Counsyl

Jun 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.65

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over