17-39470710-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016507.4(CDK12):c.1047-169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,978 control chromosomes in the GnomAD database, including 33,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (33078 hom., cov: 31)
• Consequence: CDK12 NM_016507.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 17-39470710-G-A is Benign according to our data. Variant chr17-39470710-G-A is described in ClinVar as [Benign]. Clinvar id is 1283081.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
CDK12	NM_016507.4	c.1047-169G>A		intron_variant		ENST00000447079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK12	ENST00000447079.6	c.1047-169G>A		intron_variant		1	NM_016507.4	P4
CDK12	ENST00000430627.6	c.1047-169G>A		intron_variant		1		A1
CDK12	ENST00000584632.5	c.1047-172G>A		intron_variant		5
CDK12	ENST00000559663.2	c.1047-169G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95985 AN: 151860 Hom.: 33073 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.632 AC: 96025 AN: 151978 Hom.: 33078 Cov.: 31 AF XY: 0.639 AC XY: 47441 AN XY: 74284

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.645

Alfa AF: 0.693 Hom.: 8482

Bravo AF: 0.600

Asia WGS AF: 0.764 AC: 2657 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.4
Dann	Benign	0.33

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: rs11657899; hg19: chr17-37626963;