rs7706902

Positions:

• chr5-69261475-G-A
• chr5-69261475-G-C

Variant summary

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

The NM_001799.4(CDK7):​c.528-730G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 149,382 control chromosomes in the GnomAD database, including 6,466 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 (6466 hom., cov: 30)
• Consequence: CDK7 NM_001799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK7	NM_001799.4	c.528-730G>A		intron_variant		ENST00000256443.8	NP_001790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8	c.528-730G>A		intron_variant		1	NM_001799.4	ENSP00000256443	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 41998 AN: 149266 Hom.: 6462 Cov.: 30

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.281 AC: 42011 AN: 149382 Hom.: 6466 Cov.: 30 AF XY: 0.284 AC XY: 20665 AN XY: 72756

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.293

Alfa AF: 0.305 Hom.: 957

Bravo AF: 0.269

Asia WGS AF: 0.356 AC: 1234 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7706902; hg19: chr5-68557302;