5-69235426-C-T

Position:

• chr5-69235426-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001799.4(CDK7):​c.99C>T​(p.Asn33=) variant causes a synonymous 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. 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_001799.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.526 with no splicing effect.
• 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	UniProt
CDK7	NM_001799.4	c.99C>T	p.Asn33=	synonymous_variant	2/12	ENST00000256443.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK7	ENST00000256443.8	c.99C>T	p.Asn33=	synonymous_variant	2/12	1	NM_001799.4	P1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91429 AN: 151992 Hom.: 28005 Cov.: 33

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

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.: 31 AF XY: 0.551 AC XY: 394982 AN XY: 716274

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.: 33 AF XY: 0.606 AC XY: 45049 AN XY: 74380

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	13
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

Other links and lift over

dbSNP: rs2972388; hg19: chr5-68531253; COSMIC: COSV56512190;