chr5-69261475-G-A

Variant names:

• chr5-69261475-G-A
• rs7706902
• NM_001799.4:c.528-730G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001799.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK7	NM_001799.4	MANE Select	c.528-730G>A		intron	N/A	NP_001790.1
	CDK7	NM_001324069.2		c.405-730G>A		intron	N/A	NP_001310998.1
	CDK7	NM_001324070.2		c.357-730G>A		intron	N/A	NP_001310999.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK7	ENST00000256443.8	TSL:1 MANE Select	c.528-730G>A		intron	N/A	ENSP00000256443.3
	CDK7	ENST00000514676.5	TSL:5	c.417-730G>A		intron	N/A	ENSP00000422737.1
	CDK7	ENST00000502604.5	TSL:5	c.249-730G>A		intron	N/A	ENSP00000422121.1

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

African (AFR) AF: 0.140 AC: 5640 AN: 40390

American (AMR) AF: 0.303 AC: 4494 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 941 AN: 3454

East Asian (EAS) AF: 0.397 AC: 2001 AN: 5038

South Asian (SAS) AF: 0.375 AC: 1758 AN: 4690

European-Finnish (FIN) AF: 0.348 AC: 3546 AN: 10182

Middle Eastern (MID) AF: 0.345 AC: 100 AN: 290

European-Non Finnish (NFE) AF: 0.333 AC: 22461 AN: 67532

Other (OTH) AF: 0.293 AC: 603 AN: 2056

Alfa AF: 0.297 Hom.: 962

Bravo AF: 0.269

Asia WGS AF: 0.356 AC: 1234 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7706902; hg19: chr5-68557302;