8-116857259-C-T

Position:

chr8-116857259-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006265.3(RAD21):c.688+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,596,092 control chromosomes in the GnomAD database, including 4,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2052 hom., cov: 33)

Exomes 𝑓: 0.035 ( 2906 hom. )

Consequence

RAD21
NM_006265.3 splice_region, intron

Scores

Splicing: ADA: 0.00003647

Clinical Significance

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

Conservation

PhyloP100: 0.0230

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:

RAD21 (HGNC:):

RAD21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-116857259-C-T is Benign according to our data. Variant chr8-116857259-C-T is described in ClinVar as [Benign]. Clinvar id is 159808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD21	NM_006265.3 linkuse as main transcript	c.688+8G>A		splice_region_variant, intron_variant		ENST00000297338.7	NP_006256.1	O60216A0A024R9J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7 linkuse as main transcript	c.688+8G>A		splice_region_variant, intron_variant		1	NM_006265.3	ENSP00000297338.2		O60216

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16796

AN:

152014

Hom.:

2044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0612

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.0420

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0956

GnomAD3 exomes

AF:

0.0632

AC:

15747

AN:

249250

Hom.:

1206

AF XY:

0.0555

AC XY:

7474

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.0864

Gnomad ASJ exome

AF:

0.0632

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.0387

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0493

GnomAD4 exome

AF:

0.0354

AC:

51096

AN:

1443960

Hom.:

2906

Cov.:

AF XY:

0.0346

AC XY:

24896

AN XY:

718980

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.0849

Gnomad4 ASJ exome

AF:

0.0597

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.0384

Gnomad4 FIN exome

AF:

0.0156

Gnomad4 NFE exome

AF:

0.0195

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.111

AC:

16835

AN:

152132

Hom.:

2052

Cov.:

AF XY:

0.108

AC XY:

8042

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.0612

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.0420

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.0230

Gnomad4 OTH

AF:

0.0970

Alfa

AF:

0.0406

Hom.:

625

Bravo

AF:

0.124

Asia WGS

AF:

0.115

AC:

398

AN:

3478

EpiCase

AF:

0.0268

EpiControl

AF:

0.0301

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 02, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 04, 2017	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. -

Cornelia de Lange syndrome 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Mungan syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.4

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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