rs7322113

Variant names:

• chr13-26268070-T-C
• rs7322113
• NM_001260.3:c.128+13301T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001260.3(CDK8):​c.128+13301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,136 control chromosomes in the GnomAD database, including 2,634 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 0.11 (2634 hom., cov: 32)
• Consequence: CDK8 NM_001260.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK8	NM_001260.3	c.128+13301T>C		intron_variant	Intron 1 of 12	ENST00000381527.8	NP_001251.1
CDK8	NM_001318368.2	c.128+13301T>C		intron_variant	Intron 1 of 12		NP_001305297.1
CDK8	NM_001346501.2	c.-334+13301T>C		intron_variant	Intron 1 of 11		NP_001333430.1
CDK8	XM_047430033.1	c.-103+13301T>C		intron_variant	Intron 1 of 13		XP_047285989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK8	ENST00000381527.8	c.128+13301T>C		intron_variant	Intron 1 of 12	1	NM_001260.3	ENSP00000370938.3
CDK8	ENST00000536792.5	n.128+13301T>C		intron_variant	Intron 1 of 11	1		ENSP00000437696.1
CDK8	ENST00000700501.1	n.128+13301T>C		intron_variant	Intron 1 of 11			ENSP00000515024.1
CDK8	ENST00000700502.1	n.216+12865T>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16405 AN: 152020 Hom.: 2626 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.108 AC: 16446 AN: 152136 Hom.: 2634 Cov.: 32 AF XY: 0.103 AC XY: 7699 AN XY: 74390

African (AFR) AF: 0.353 AC: 14600 AN: 41418

American (AMR) AF: 0.0433 AC: 662 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4822

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 818 AN: 68020

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0617 Hom.: 288

Bravo AF: 0.124

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7322113; hg19: chr13-26842207;