Variant 9-127789170-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001261.4(CDK9):c.754-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,554,136 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 14 hom. )

Consequence

CDK9
NM_001261.4 splice_region, intron

Scores

Splicing: ADA: 0.00006251

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.933

Variant links:

Genes affected

CDK9 (HGNC:1780): (cyclin dependent kinase 9) The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. [provided by RefSeq, Jul 2008]

CDK9 links:

CDK9 (HGNC:):

CDK9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 9-127789170-C-T is Benign according to our data. Variant chr9-127789170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037641.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 448 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK9	NM_001261.4 linkuse as main transcript	c.754-8C>T		splice_region_variant, intron_variant		ENST00000373264.5	NP_001252.1	P50750-1A0A024R880

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK9	ENST00000373264.5 linkuse as main transcript	c.754-8C>T		splice_region_variant, intron_variant		1	NM_001261.4	ENSP00000362361.4		P50750-1
CDK9	ENST00000498339.1 linkuse as main transcript	n.272-8C>T		splice_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

449

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00328

AC:

700

AN:

213244

Hom.:

AF XY:

0.00323

AC XY:

369

AN XY:

114256

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.000618

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000977

Gnomad FIN exome

AF:

0.00444

Gnomad NFE exome

AF:

0.00524

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00482

AC:

6761

AN:

1401866

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

3124

AN XY:

689820

show subpopulations

Gnomad4 AFR exome

AF:

0.000915

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.000662

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.000883

Gnomad4 FIN exome

AF:

0.00471

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00403

GnomAD4 genome

AF:

0.00294

AC:

448

AN:

152270

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.00485

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00359

Hom.:

Bravo

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDK9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.0

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over