8-116867092-A-G

Position:

• chr8-116867092-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.-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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.239

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
RAD21	NM_006265.3	c.-32-331T>C		intron_variant		ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.-32-331T>C		intron_variant		1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24941 AN: 151998 Hom.: 2499 Cov.: 32

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

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.0781

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.164 AC: 24963 AN: 152116 Hom.: 2501 Cov.: 32 AF XY: 0.164 AC XY: 12173 AN XY: 74382

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.165

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.79

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: rs16924; hg19: chr8-117879331;