chr8-116866452-C-T

Variant names:

• chr8-116866452-C-T
• rs16889040
• NM_006265.3:c.144+134G>A

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.144+134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 712,942 control chromosomes in the GnomAD database, including 28,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4454 hom., cov: 32)
  • Exomes 𝑓: 0.28 (23755 hom.)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.205

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=-0.9).
• BP6: Variant 8-116866452-C-T is Benign according to our data. Variant chr8-116866452-C-T is described in ClinVar as [Benign]. Clinvar id is 670486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3	c.144+134G>A		intron_variant	Intron 2 of 13	ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.144+134G>A		intron_variant	Intron 2 of 13	1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33170 AN: 151882 Hom.: 4453 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.281 AC: 157396 AN: 560942 Hom.: 23755 AF XY: 0.287 AC XY: 82017 AN XY: 286244

Gnomad4 AFR exome AF: 0.0591

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.218 AC: 33181 AN: 152000 Hom.: 4454 Cov.: 32 AF XY: 0.224 AC XY: 16663 AN XY: 74310

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.191

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: 0.252 Hom.: 653

Bravo AF: 0.197

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.90
CADD	Benign	5.4
DANN	Benign	0.35

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: rs16889040; hg19: chr8-117878691;