rs2691180

chr6-110630803-A-C

Variant summary

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

The NM_015076.5(CDK19):c.646+1227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,150 control chromosomes in the GnomAD database, including 3,908 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 0.22 (3908 hom., cov: 33)
• Consequence: CDK19 NM_015076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

CDK19 (HGNC:19338): (cyclin dependent kinase 19) This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK19	NM_015076.5	c.646+1227T>G		intron_variant		ENST00000368911.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK19	ENST00000368911.8	c.646+1227T>G		intron_variant		1	NM_015076.5	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33631 AN: 152034 Hom.: 3912 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.221 AC: 33638 AN: 152150 Hom.: 3908 Cov.: 33 AF XY: 0.223 AC XY: 16589 AN XY: 74378

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.213

Alfa AF: 0.211 Hom.: 559

Bravo AF: 0.221

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.6
Dann	Benign	0.81

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: rs2691180; hg19: chr6-110952006;