rs16888927

chr8-116857221-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006265.3(RAD21):c.688+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,525,326 control chromosomes in the GnomAD database, including 64,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4466 hom., cov: 33)
  • Exomes 𝑓: 0.29 (60482 hom.)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0830

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-116857221-A-G is Benign according to our data. Variant chr8-116857221-A-G is described in ClinVar as [Benign]. Clinvar id is 675063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD21	NM_006265.3	c.688+46T>C		intron_variant		ENST00000297338.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD21	ENST00000297338.7	c.688+46T>C		intron_variant		1	NM_006265.3	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33206 AN: 152064 Hom.: 4465 Cov.: 33

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.274 AC: 64022 AN: 233322 Hom.: 10203 AF XY: 0.290 AC XY: 36605 AN XY: 126036

Gnomad AFR exome AF: 0.0589

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.482

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.288 AC: 395024 AN: 1373142 Hom.: 60482 Cov.: 21 AF XY: 0.294 AC XY: 201279 AN XY: 684472

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.218 AC: 33217 AN: 152184 Hom.: 4466 Cov.: 33 AF XY: 0.224 AC XY: 16675 AN XY: 74386

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.210

Alfa AF: 0.244 Hom.: 873

Bravo AF: 0.197

Asia WGS AF: 0.306 AC: 1066 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.3
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs16888927; hg19: chr8-117869460;