rs1050838

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006265.3(RAD21):c.1440T>C(p.Ala480Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,609,546 control chromosomes in the GnomAD database, including 23,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1772 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21703 hom. )

Consequence

RAD21
NM_006265.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.942

Publications

28 publications found

Variant links:

Genes affected

RAD21 (HGNC:9811): (RAD21 cohesin complex component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]

RAD21 Gene-Disease associations (from GenCC):

Cornelia de Lange syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Cornelia de Lange syndrome 4
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Mungan syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

RAD21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-116851978-A-G is Benign according to our data. Variant chr8-116851978-A-G is described in ClinVar as Benign. ClinVar VariationId is 159805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.942 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3 link	c.1440T>C	p.Ala480Ala	synonymous_variant	Exon 11 of 14	ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7 link	c.1440T>C	p.Ala480Ala	synonymous_variant	Exon 11 of 14	1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20675

AN:

152062

Hom.:

1767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.178

AC:

44578

AN:

250998

AF XY:

0.179

show subpopulations

Gnomad AFR exome

AF:

0.0290

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.169

AC:

246021

AN:

1457366

Hom.:

21703

Cov.:

AF XY:

0.170

AC XY:

123575

AN XY:

724814

show subpopulations

African (AFR)

AF:

0.0276

AC:

923

AN:

33424

American (AMR)

AF:

0.249

AC:

11129

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5648

AN:

26008

East Asian (EAS)

AF:

0.168

AC:

6644

AN:

39620

South Asian (SAS)

AF:

0.206

AC:

17751

AN:

85962

European-Finnish (FIN)

AF:

0.167

AC:

8902

AN:

53302

Middle Eastern (MID)

AF:

0.184

AC:

1031

AN:

5594

European-Non Finnish (NFE)

AF:

0.166

AC:

184052

AN:

1108654

Other (OTH)

AF:

0.165

AC:

9941

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10024

20049

30073

40098

50122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6566

13132

19698

26264

32830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.136

AC:

20697

AN:

152180

Hom.:

1772

Cov.:

AF XY:

0.139

AC XY:

10325

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0315

AC:

1310

AN:

41554

American (AMR)

AF:

0.211

AC:

3225

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

780

AN:

3470

East Asian (EAS)

AF:

0.174

AC:

898

AN:

5172

South Asian (SAS)

AF:

0.199

AC:

961

AN:

4822

European-Finnish (FIN)

AF:

0.170

AC:

1796

AN:

10592

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11299

AN:

67970

Other (OTH)

AF:

0.136

AC:

288

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

897

1794

2691

3588

4485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

6602

Bravo

AF:

0.134

Asia WGS

AF:

0.183

AC:

635

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 06, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cornelia de Lange syndrome 4

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mungan syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.8

(source)

DANN

Benign

0.62

PhyloP100

-0.94

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over