rs7503195

Positions:

• chr17-39566262-G-A
• chr17-39566262-G-T

Variant summary

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

The XM_011524893.3(CDK12):​c.*702-526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,032 control chromosomes in the GnomAD database, including 9,718 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 0.33 (9718 hom., cov: 32)
• Consequence: CDK12 XM_011524893.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK12	XM_011524893.3	c.*702-526G>A		intron_variant
CDK12	XM_011524894.3	c.*652-526G>A		intron_variant
CDK12	XM_011524895.3	c.*897-526G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK12	ENST00000559663.2	c.*872-526G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50536 AN: 151914 Hom.: 9715 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.332 AC: 50535 AN: 152032 Hom.: 9718 Cov.: 32 AF XY: 0.336 AC XY: 24960 AN XY: 74294

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.360

Alfa AF: 0.379 Hom.: 4757

Bravo AF: 0.318

Asia WGS AF: 0.457 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7503195; hg19: chr17-37722515;