8-116847913-T-C

Position:

• chr8-116847913-T-C

Variant summary

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

The ENST00000297338.7(RAD21):​c.1705-222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,186 control chromosomes in the GnomAD database, including 1,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1761 hom., cov: 32)
• Consequence: RAD21 ENST00000297338.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.141

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]

LOC112268030 (HGNC:):

UTP23 (HGNC:28224): (UTP23 small subunit processome component) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-116847913-T-C is Benign according to our data. Variant chr8-116847913-T-C is described in ClinVar as [Benign]. Clinvar id is 669108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD21	NM_006265.3	c.1705-222A>G		intron_variant		ENST00000297338.7	NP_006256.1
LOC112268030	XR_002956724.2	n.761-975T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.1705-222A>G		intron_variant		1	NM_006265.3	ENSP00000297338	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20637 AN: 152068 Hom.: 1758 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20647 AN: 152186 Hom.: 1761 Cov.: 32 AF XY: 0.138 AC XY: 10291 AN XY: 74388

Gnomad4 AFR AF: 0.0306

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.136

Alfa AF: 0.162 Hom.: 347

Bravo AF: 0.133

Asia WGS AF: 0.178 AC: 618 AN: 3478

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	-0.93
CADD	Benign	2.3
DANN	Benign	0.61

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: rs16888887; hg19: chr8-117860152;