7-92607515-A-G

Position:

• chr7-92607515-A-G

Variant summary

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

The NM_001145306.2(CDK6):​c.*7625T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 232,722 control chromosomes in the GnomAD database, including 4,637 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 0.20 (3028 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1609 hom.)
• Consequence: CDK6 NM_001145306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

CDK6 (HGNC:1777): (cyclin dependent kinase 6) The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.*7625T>C		3_prime_UTR_variant	8/8	ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.*7625T>C		3_prime_UTR_variant	8/8		NP_001250.1
CDK6	XM_047419716.1	c.*7625T>C		3_prime_UTR_variant	8/8		XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.*7625T>C		3_prime_UTR_variant	8/8	1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8	c.*7625T>C		3_prime_UTR_variant	8/8	1		ENSP00000265734	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29697 AN: 152002 Hom.: 3026 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.196 AC: 15830 AN: 80602 Hom.: 1609 Cov.: 0 AF XY: 0.196 AC XY: 7260 AN XY: 37050

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.0860

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.195 AC: 29719 AN: 152120 Hom.: 3028 Cov.: 32 AF XY: 0.194 AC XY: 14414 AN XY: 74366

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.201

Alfa AF: 0.203 Hom.: 3406

Bravo AF: 0.197

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.71

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: rs4272; hg19: chr7-92236829;