rs12656449

chr5-69273660-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+619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,212 control chromosomes in the GnomAD database, including 1,102 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 0.11 (1102 hom., cov: 33)
• Consequence: CDK7 NM_001799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK7	NM_001799.4	c.864+619G>A		intron_variant		ENST00000256443.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK7	ENST00000256443.8	c.864+619G>A		intron_variant		1	NM_001799.4	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16546 AN: 152094 Hom.: 1101 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0979

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

GnomAD4 genome AF: 0.109 AC: 16549 AN: 152212 Hom.: 1102 Cov.: 33 AF XY: 0.110 AC XY: 8165 AN XY: 74424

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.0442

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.0969

Alfa AF: 0.0876 Hom.: 632

Bravo AF: 0.111

Asia WGS AF: 0.140 AC: 488 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.2
Dann	Benign	0.44

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: rs12656449; hg19: chr5-68569487;