Variant chr9-127788208-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001261.4(CDK9):c.433-6C>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 0.00909 in 1,613,898 control chromosomes in the GnomAD database, including 1,145 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.047 ( 585 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 560 hom. )

Consequence

CDK9
NM_001261.4 splice_region, intron

Scores

Splicing: ADA: 0.00001668

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.429

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-127788208-C-T is Benign according to our data. Variant chr9-127788208-C-T is described in ClinVar as [Benign]. Clinvar id is 3055715.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK9	NM_001261.4 linkuse as main transcript	c.433-6C>T		splice_region_variant, intron_variant		ENST00000373264.5	NP_001252.1	P50750-1A0A024R880

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CDK9	ENST00000373264.5 linkuse as main transcript	c.433-6C>T	splice_region_variant, intron_variant	1	NM_001261.4	ENSP00000362361.4	P50750-1
CDK9	ENST00000480353.5 linkuse as main transcript	n.508-6C>T	splice_region_variant, intron_variant	2
CDK9	ENST00000491521.1 linkuse as main transcript	n.277-6C>T	splice_region_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7066

AN:

152218

Hom.:

582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0123

AC:

3065

AN:

250196

Hom.:

228

AF XY:

0.00936

AC XY:

1268

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.00703

Gnomad ASJ exome

AF:

0.000599

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000550

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00519

AC:

7583

AN:

1461562

Hom.:

560

Cov.:

AF XY:

0.00457

AC XY:

3322

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.00848

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.000391

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.0465

AC:

7091

AN:

152336

Hom.:

585

Cov.:

AF XY:

0.0451

AC XY:

3361

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0309

Hom.:

178

Bravo

AF:

0.0540

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDK9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2019

This variant is classified as 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

-0.84

CADD

Benign

1.1

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.022

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