13-26412598-T-C

Variant names:

• chr13-26412598-T-C
• rs1410280
• ENST00000700505.1:n.1075-7609T>C

Variant summary

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

The ENST00000700505.1(CDK8):​n.1075-7609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,042 control chromosomes in the GnomAD database, including 54,548 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 0.83 (54548 hom., cov: 32)
• Consequence: CDK8 ENST00000700505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK8	ENST00000700505.1	n.1075-7609T>C		intron_variant	Intron 10 of 10

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126867 AN: 151924 Hom.: 54542 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.972

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.835 AC: 126918 AN: 152042 Hom.: 54548 Cov.: 32 AF XY: 0.837 AC XY: 62171 AN XY: 74302

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.870

Alfa AF: 0.918 Hom.: 77953

Bravo AF: 0.830

Asia WGS AF: 0.944 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1410280; hg19: chr13-26986735;