rs12656449

Variant names:

• chr5-69273660-G-A
• rs12656449
• NM_001799.4:c.864+619G>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.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
• Publications: 7 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]

CCDC125 (HGNC:28924): (coiled-coil domain containing 125) Enables identical protein binding activity. Involved in activation of GTPase activity; negative regulation of Rho protein signal transduction; and negative regulation of cell motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDK7	NM_001799.4	c.864+619G>A		intron_variant	Intron 10 of 11	ENST00000256443.8	NP_001790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8	c.864+619G>A		intron_variant	Intron 10 of 11	1	NM_001799.4	ENSP00000256443.3

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

African (AFR) AF: 0.179 AC: 7418 AN: 41514

American (AMR) AF: 0.0915 AC: 1399 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3468

East Asian (EAS) AF: 0.0442 AC: 229 AN: 5180

South Asian (SAS) AF: 0.187 AC: 901 AN: 4822

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5493 AN: 68008

Other (OTH) AF: 0.0969 AC: 205 AN: 2116

Alfa AF: 0.0894 Hom.: 815

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
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12656449; hg19: chr5-68569487;