chr5-69272148-C-T

Position:

• chr5-69272148-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001799.4(CDK7):​c.715-744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,942 control chromosomes in the GnomAD database, including 6,488 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 0.28 (6488 hom., cov: 31)
• Consequence: CDK7 NM_001799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK7	NM_001799.4	c.715-744C>T		intron_variant		ENST00000256443.8	NP_001790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8	c.715-744C>T		intron_variant		1	NM_001799.4	ENSP00000256443.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42431 AN: 151824 Hom.: 6486 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42438 AN: 151942 Hom.: 6488 Cov.: 31 AF XY: 0.282 AC XY: 20947 AN XY: 74266

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.292

Alfa AF: 0.303 Hom.: 1284

Bravo AF: 0.269

Asia WGS AF: 0.352 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.75

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: rs4423955; hg19: chr5-68567975;