ENST00000700505.1:n.1075-7609T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CDK8 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypotonia and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000700505.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK8	ENST00000700505.1		n.1075-7609T>C		intron	N/A

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

African (AFR) AF: 0.606 AC: 25169 AN: 41518

American (AMR) AF: 0.916 AC: 14003 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3196 AN: 3468

East Asian (EAS) AF: 0.990 AC: 5121 AN: 5172

South Asian (SAS) AF: 0.919 AC: 4437 AN: 4826

European-Finnish (FIN) AF: 0.864 AC: 9102 AN: 10536

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62903 AN: 67928

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.906 Hom.: 98258

Bravo AF: 0.830

Asia WGS AF: 0.944 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.64
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1410280; hg19: chr13-26986735;