5-69235426-C-T

Variant names:

• chr5-69235426-C-T
• rs2972388
• NM_001799.4:c.99C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDK7	NM_001799.4	c.99C>T	p.Asn33Asn	synonymous_variant	Exon 2 of 12	ENST00000256443.8	NP_001790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8	c.99C>T	p.Asn33Asn	synonymous_variant	Exon 2 of 12	1	NM_001799.4	ENSP00000256443.3

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

GnomAD2 exomes AF: 0.580 AC: 145360 AN: 250598 AF XY: 0.578

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 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 AC: 23898 AN: 32898

Gnomad4 AMR exome AF: 0.646 AC: 28804 AN: 44570

Gnomad4 ASJ exome AF: 0.536 AC: 13925 AN: 25994

Gnomad4 EAS exome AF: 0.569 AC: 22525 AN: 39594

Gnomad4 SAS exome AF: 0.656 AC: 56091 AN: 85554

Gnomad4 FIN exome AF: 0.577 AC: 30798 AN: 53388

Gnomad4 NFE exome AF: 0.528 AC: 575857 AN: 1090022

Gnomad4 Remaining exome AF: 0.559 AC: 33295 AN: 59526

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 AC: 0.713804 AN: 0.713804

Gnomad4 AMR AF: 0.634 AC: 0.634316 AN: 0.634316

Gnomad4 ASJ AF: 0.528 AC: 0.527938 AN: 0.527938

Gnomad4 EAS AF: 0.512 AC: 0.51157 AN: 0.51157

Gnomad4 SAS AF: 0.653 AC: 0.653049 AN: 0.653049

Gnomad4 FIN AF: 0.582 AC: 0.581932 AN: 0.581932

Gnomad4 NFE AF: 0.536 AC: 0.535701 AN: 0.535701

Gnomad4 OTH AF: 0.580 AC: 0.580492 AN: 0.580492

Alfa AF: 0.551 Hom.: 17135

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
Mutation Taster		=277/23	polymorphism (auto)

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;