Variant chr8-116854479-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006265.3(RAD21):c.938-11T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,595,000 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 31 hom. )

Consequence

RAD21
NM_006265.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001232

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.71

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-116854479-A-G is Benign according to our data. Variant chr8-116854479-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 159809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-116854479-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00397 (605/152248) while in subpopulation NFE AF= 0.00763 (519/68006). AF 95% confidence interval is 0.00709. There are 3 homozygotes in gnomad4. There are 256 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD21	NM_006265.3 linkuse as main transcript	c.938-11T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000297338.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD21	ENST00000297338.7 linkuse as main transcript	c.938-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006265.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

605

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00373

AC:

932

AN:

249888

Hom.:

AF XY:

0.00357

AC XY:

482

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000961

Gnomad ASJ exome

AF:

0.00481

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00279

Gnomad NFE exome

AF:

0.00677

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00544

AC:

7847

AN:

1442752

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

3802

AN XY:

719142

show subpopulations

Gnomad4 AFR exome

AF:

0.000790

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00314

Gnomad4 NFE exome

AF:

0.00662

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00397

AC:

605

AN:

152248

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00763

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.00356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 14, 2014

- -

Cornelia de Lange syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.010

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