rs11078903

Positions:

• chr17-39475671-G-A
• chr17-39475671-G-C
• chr17-39475671-G-T

Variant summary

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

The NM_016507.4(CDK12):​c.1931+3908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 150,832 control chromosomes in the GnomAD database, including 33,031 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 0.63 (33031 hom., cov: 26)
• Consequence: CDK12 NM_016507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

CDK12 (HGNC:24224): (cyclin dependent kinase 12) Enables RNA polymerase II CTD heptapeptide repeat kinase activity and cyclin binding activity. Involved in phosphorylation of RNA polymerase II C-terminal domain; protein autophosphorylation; and regulation of MAP kinase activity. Located in nuclear speck. Part of cyclin K-CDK12 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK12	NM_016507.4	c.1931+3908G>A		intron_variant		ENST00000447079.6	NP_057591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK12	ENST00000447079.6	c.1931+3908G>A		intron_variant		1	NM_016507.4	ENSP00000398880.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 95617 AN: 150714 Hom.: 33033 Cov.: 26

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.634 AC: 95647 AN: 150832 Hom.: 33031 Cov.: 26 AF XY: 0.641 AC XY: 47149 AN XY: 73596

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.647

Alfa AF: 0.680 Hom.: 4428

Bravo AF: 0.602

Asia WGS AF: 0.763 AC: 2652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.73

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: rs11078903; hg19: chr17-37631924;