Variant chr5-69235426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001324071.2(CDK7):c.65C>T(p.Thr22Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,589,374 control chromosomes in the GnomAD database, including 247,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 28036 hom., cov: 33)

Exomes 𝑓: 0.55 ( 219345 hom. )

Consequence

CDK7
NM_001324071.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.526

Variant links:

Genes affected

CDK7 (HGNC:1778): (cyclin dependent kinase 7) 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 Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle. [provided by RefSeq, Jul 2008]

CDK7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK7	NM_001799.4 link	c.99C>T	p.Asn33Asn	synonymous_variant	2/12	ENST00000256443.8	NP_001790.1	P50613A0A0S2Z3F9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8 link	c.99C>T	p.Asn33Asn	synonymous_variant	2/12	1	NM_001799.4	ENSP00000256443.3		P50613

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91429

AN:

151992

Hom.:

28005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.714

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.581

GnomAD3 exomes

AF:

0.580

AC:

145360

AN:

250598

Hom.:

42714

AF XY:

0.578

AC XY:

78282

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.544

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.657

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.538

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.549

AC:

788383

AN:

1437264

Hom.:

219345

Cov.:

AF XY:

0.551

AC XY:

394982

AN XY:

716274

show subpopulations

Gnomad4 AFR exome

AF:

0.726

Gnomad4 AMR exome

AF:

0.646

Gnomad4 ASJ exome

AF:

0.536

Gnomad4 EAS exome

AF:

0.569

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.528

Gnomad4 OTH exome

AF:

0.559

GnomAD4 genome

AF:

0.602

AC:

91506

AN:

152110

Hom.:

28036

Cov.:

AF XY:

0.606

AC XY:

45049

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.714

Gnomad4 AMR

AF:

0.634

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.653

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.580

Alfa

AF:

0.547

Hom.:

14943

Bravo

AF:

0.606

Asia WGS

AF:

0.593

AC:

2066

AN:

3478

EpiCase

AF:

0.534

EpiControl

AF:

0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.89

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over