5-69274130-G-A

Position:

• chr5-69274130-G-A

Variant summary

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

The NM_001799.4(CDK7):​c.864+1089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,034 control chromosomes in the GnomAD database, including 6,840 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 0.29 (6840 hom., cov: 32)
• Consequence: CDK7 NM_001799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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]

CCDC125 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK7	NM_001799.4	c.864+1089G>A		intron_variant		ENST00000256443.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK7	ENST00000256443.8	c.864+1089G>A		intron_variant		1	NM_001799.4	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43445 AN: 151918 Hom.: 6836 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.286 AC: 43457 AN: 152034 Hom.: 6840 Cov.: 32 AF XY: 0.289 AC XY: 21430 AN XY: 74278

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.297

Alfa AF: 0.319 Hom.: 5625

Bravo AF: 0.279

Asia WGS AF: 0.372 AC: 1290 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.83

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: rs6865178; hg19: chr5-68569957; COSMIC: COSV56512692; COSMIC: COSV56512692;