17-39461967-C-T

Position:

• chr17-39461967-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016507.4(CDK12):​c.-105C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (46 hom., cov: 0)
  • Exomes 𝑓: 0.029 (317 hom.)
• Consequence: CDK12 NM_016507.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-39461967-C-T is Benign according to our data. Variant chr17-39461967-C-T is described in ClinVar as [Benign]. Clinvar id is 1252879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK12	NM_016507.4	c.-105C>T		5_prime_UTR_variant	1/14	ENST00000447079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK12	ENST00000447079.6	c.-105C>T		5_prime_UTR_variant	1/14	1	NM_016507.4	P4
CDK12	ENST00000430627.6	c.-105C>T		5_prime_UTR_variant	1/14	1		A1
CDK12	ENST00000584632.5	c.-105C>T		5_prime_UTR_variant	1/13	5
CDK12	ENST00000559663.2	c.-105C>T		5_prime_UTR_variant, NMD_transcript_variant	1/21	5

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 3194 AN: 34768 Hom.: 46 Cov.: 0

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.00227

Gnomad SAS AF: 0.0200

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0973

GnomAD4 exome AF: 0.0290 AC: 19308 AN: 665270 Hom.: 317 Cov.: 10 AF XY: 0.0276 AC XY: 9461 AN XY: 342570

Gnomad4 AFR exome AF: 0.00657

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.00842

Gnomad4 EAS exome AF: 0.0000466

Gnomad4 SAS exome AF: 0.00509

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0337

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.0918 AC: 3194 AN: 34804 Hom.: 46 Cov.: 0 AF XY: 0.0906 AC XY: 1550 AN XY: 17106

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0243

Gnomad4 EAS AF: 0.00228

Gnomad4 SAS AF: 0.0200

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0253 Hom.: 7

Bravo AF: 0.0206

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs192819848; hg19: chr17-37618220;