Variant chr14-99500873-TAAG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001099402.2(CCNK):c.517+8_517+10del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,504,068 control chromosomes in the GnomAD database, including 7 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 4 hom. )

Consequence

CCNK
NM_001099402.2 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

CCDC85C (HGNC:35459): (coiled-coil domain containing 85C) Predicted to be involved in cerebral cortex development. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CCDC85C links:

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 14-99500873-TAAG-T is Benign according to our data. Variant chr14-99500873-TAAG-T is described in ClinVar as [Benign]. Clinvar id is 720140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CCDC85C	NM_001144995.2 linkuse as main transcript	c.14370_14372del	3_prime_UTR_variant	6/6	ENST00000380243.9
CCNK	NM_001099402.2 linkuse as main transcript	c.517+8_517+10del	splice_donor_5th_base_variant, intron_variant		ENST00000389879.9
CCNK	XM_005268154.5 linkuse as main transcript	c.517+8_517+10del	splice_donor_5th_base_variant, intron_variant
CCNK	XM_047431839.1 linkuse as main transcript	c.517+8_517+10del	splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC85C	ENST00000380243.9 linkuse as main transcript	c.14370_14372del		3_prime_UTR_variant	6/6	5	NM_001144995.2	P1
CCNK	ENST00000389879.9 linkuse as main transcript	c.517+8_517+10del		splice_donor_5th_base_variant, intron_variant		5	NM_001099402.2	P1	O75909-3

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

281

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00254

AC:

365

AN:

143442

Hom.:

AF XY:

0.00216

AC XY:

163

AN XY:

75530

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000952

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000681

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.000453

AC:

613

AN:

1351722

Hom.:

AF XY:

0.000410

AC XY:

274

AN XY:

668816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000667

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00198

Gnomad4 SAS exome

AF:

0.0000403

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000498

Gnomad4 OTH exome

AF:

0.000585

GnomAD4 genome

AF:

0.00186

AC:

283

AN:

152346

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000800

Hom.:

Bravo

AF:

0.00329

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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