rs11078903

Variant names:

• chr17-39475671-G-A
• rs11078903
• NM_016507.4:c.1931+3908G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

CDK12 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDK12	NM_016507.4	c.1931+3908G>A		intron_variant	Intron 2 of 13	ENST00000447079.6	NP_057591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK12	ENST00000447079.6	c.1931+3908G>A		intron_variant	Intron 2 of 13	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

African (AFR) AF: 0.339 AC: 13882 AN: 40900

American (AMR) AF: 0.657 AC: 9898 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3466

East Asian (EAS) AF: 0.728 AC: 3685 AN: 5064

South Asian (SAS) AF: 0.889 AC: 4256 AN: 4786

European-Finnish (FIN) AF: 0.839 AC: 8741 AN: 10424

Middle Eastern (MID) AF: 0.712 AC: 205 AN: 288

European-Non Finnish (NFE) AF: 0.745 AC: 50577 AN: 67856

Other (OTH) AF: 0.647 AC: 1351 AN: 2088

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
PhyloP100		-1.7
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: rs11078903; hg19: chr17-37631924;