rs718652

Positions:

• chr13-26406453-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000700505.1(CDK8):​n.1074+2298A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,848 control chromosomes in the GnomAD database, including 14,701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14701 hom., cov: 31)
• Consequence: CDK8 ENST00000700505.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868

Genes affected

CDK8 (HGNC:1779): (cyclin dependent kinase 8) This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK8	ENST00000700505.1	n.1074+2298A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62706 AN: 151730 Hom.: 14716 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.413 AC: 62664 AN: 151848 Hom.: 14701 Cov.: 31 AF XY: 0.415 AC XY: 30802 AN XY: 74214

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.436

Alfa AF: 0.469 Hom.: 2339

Bravo AF: 0.391

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.013
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs718652; hg19: chr13-26980590;