Variant chr14-99495493-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001099402.2(CCNK):c.280-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,603,206 control chromosomes in the GnomAD database, including 252,622 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 (★★).

Frequency

Genomes: 𝑓 0.50 ( 19337 hom., cov: 32)

Exomes 𝑓: 0.56 ( 233285 hom. )

Consequence

CCNK
NM_001099402.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008483

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.906

Variant links:

Genes affected

CCNK (HGNC:1596): (cyclin K) The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]

CCNK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-99495493-T-C is Benign according to our data. Variant chr14-99495493-T-C is described in ClinVar as [Benign]. Clinvar id is 1192628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CCNK	NM_001099402.2 linkuse as main transcript	c.280-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000389879.9
CCNK	XM_005268154.5 linkuse as main transcript	c.280-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CCNK	XM_047431839.1 linkuse as main transcript	c.280-5T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.280-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001099402.2	P1	O75909-3

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75365

AN:

151856

Hom.:

19336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.518

GnomAD3 exomes

AF:

0.503

AC:

120589

AN:

239596

Hom.:

31389

AF XY:

0.517

AC XY:

67247

AN XY:

130148

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.491

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.563

AC:

816759

AN:

1451232

Hom.:

233285

Cov.:

AF XY:

0.563

AC XY:

406481

AN XY:

721942

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.496

AC:

75380

AN:

151974

Hom.:

19337

Cov.:

AF XY:

0.491

AC XY:

36439

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.389

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.472

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.510

Gnomad4 FIN

AF:

0.493

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.517

Alfa

AF:

0.559

Hom.:

57032

Bravo

AF:

0.486

Asia WGS

AF:

0.479

AC:

1667

AN:

3478

EpiCase

AF:

0.588

EpiControl

AF:

0.593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CCNK-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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). -

Intellectual developmental disorder with hypertelorism and distinctive facies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00085

dbscSNV1_RF

Benign

0.076

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