dbSNP rs3816342: RAD21:c.481+216T>C (chr8-116858136-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.481+216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,236 control chromosomes in the GnomAD database, including 1,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1745 hom., cov: 32)

Consequence

RAD21
NM_006265.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.502

Publications

8 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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=-0.9).

BP6

Variant 8-116858136-A-G is Benign according to our data. Variant chr8-116858136-A-G is described in ClinVar as Benign. ClinVar VariationId is 668613.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006265.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	NM_006265.3	MANE Select	c.481+216T>C		intron	N/A	NP_006256.1	O60216

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD21	ENST00000297338.7	TSL:1 MANE Select	c.481+216T>C	intron	N/A	ENSP00000297338.2	O60216
RAD21	ENST00000517749.2	TSL:1	c.481+216T>C	intron	N/A	ENSP00000430273.2	O60216
RAD21	ENST00000517485.6	TSL:3	c.481+216T>C	intron	N/A	ENSP00000427923.2	O60216

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20579

AN:

152118

Hom.:

1742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.135

AC:

20589

AN:

152236

Hom.:

1745

Cov.:

AF XY:

0.138

AC XY:

10273

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0308

AC:

1282

AN:

41570

American (AMR)

AF:

0.211

AC:

3219

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

778

AN:

3472

East Asian (EAS)

AF:

0.174

AC:

902

AN:

5186

South Asian (SAS)

AF:

0.198

AC:

957

AN:

4828

European-Finnish (FIN)

AF:

0.169

AC:

1785

AN:

10578

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11240

AN:

68000

Other (OTH)

AF:

0.135

AC:

286

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

882

1763

2645

3526

4408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.143

Hom.:

261

Bravo

AF:

0.133

Asia WGS

AF:

0.178

AC:

618

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.7

(source)

DANN

Benign

0.44

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over