dbSNP rs16924: RAD21:c.-32-331T>C (chr8-116867092-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006265.3(RAD21):c.-32-331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 159,790 control chromosomes in the GnomAD database, including 2,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2501 hom., cov: 32)

Exomes 𝑓: 0.15 ( 129 hom. )

Consequence

RAD21
NM_006265.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.239

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 8-116867092-A-G is Benign according to our data. Variant chr8-116867092-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276593.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3 link	c.-32-331T>C		intron_variant	Intron 1 of 13	ENST00000297338.7	NP_006256.1	O60216A0A024R9J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7 link	c.-32-331T>C		intron_variant	Intron 1 of 13	1	NM_006265.3	ENSP00000297338.2		O60216

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24941

AN:

151998

Hom.:

2499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.0908

Gnomad FIN

AF:

0.0770

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.166

GnomAD4 exome

AF:

0.152

AC:

1168

AN:

7674

Hom.:

129

AF XY:

0.153

AC XY:

593

AN XY:

3872

show subpopulations

African (AFR)

AF:

0.291

AC:

AN:

340

American (AMR)

AF:

0.167

AC:

AN:

210

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

450

East Asian (EAS)

AF:

0.416

AC:

267

AN:

642

South Asian (SAS)

AF:

0.0800

AC:

AN:

100

European-Finnish (FIN)

AF:

0.0781

AC:

AN:

192

Middle Eastern (MID)

AF:

0.0870

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

595

AN:

5196

Other (OTH)

AF:

0.110

AC:

AN:

498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.164

AC:

24963

AN:

152116

Hom.:

2501

Cov.:

AF XY:

0.164

AC XY:

12173

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.254

AC:

10514

AN:

41474

American (AMR)

AF:

0.169

AC:

2579

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3472

East Asian (EAS)

AF:

0.375

AC:

1940

AN:

5170

South Asian (SAS)

AF:

0.0902

AC:

435

AN:

4822

European-Finnish (FIN)

AF:

0.0770

AC:

815

AN:

10582

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7452

AN:

68008

Other (OTH)

AF:

0.165

AC:

347

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1028

2056

3085

4113

5141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.132

Hom.:

201

Bravo

AF:

0.179

Asia WGS

AF:

0.186

AC:

643

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.1

(source)

DANN

Benign

0.79

PhyloP100

-0.24

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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