rs4272

Variant names:

• chr7-92607515-A-G
• rs4272
• NM_001145306.2:c.*7625T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-92607515-A-G
• chr7-92607515-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001259.8(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_001259.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 56 publications found

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]

CDK6 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microcephaly 12, primary, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001259.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	NM_001145306.2	MANE Select	c.*7625T>C		3_prime_UTR	Exon 8 of 8	NP_001138778.1
	CDK6	NM_001259.8		c.*7625T>C		3_prime_UTR	Exon 8 of 8	NP_001250.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK6	ENST00000424848.3	TSL:1 MANE Select	c.*7625T>C		3_prime_UTR	Exon 8 of 8	ENSP00000397087.3
	CDK6	ENST00000265734.8	TSL:1	c.*7625T>C		3_prime_UTR	Exon 8 of 8	ENSP00000265734.4

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

African (AFR) AF: 0.176 AC: 685 AN: 3884

American (AMR) AF: 0.212 AC: 529 AN: 2494

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 1085 AN: 5102

East Asian (EAS) AF: 0.119 AC: 1344 AN: 11284

South Asian (SAS) AF: 0.0860 AC: 60 AN: 698

European-Finnish (FIN) AF: 0.241 AC: 14 AN: 58

Middle Eastern (MID) AF: 0.205 AC: 100 AN: 488

European-Non Finnish (NFE) AF: 0.213 AC: 10622 AN: 49846

Other (OTH) AF: 0.206 AC: 1391 AN: 6748

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

African (AFR) AF: 0.177 AC: 7332 AN: 41504

American (AMR) AF: 0.192 AC: 2937 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3468

East Asian (EAS) AF: 0.106 AC: 551 AN: 5180

South Asian (SAS) AF: 0.0870 AC: 420 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2266 AN: 10552

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14749 AN: 67990

Other (OTH) AF: 0.201 AC: 423 AN: 2108

Alfa AF: 0.204 Hom.: 9727

Bravo AF: 0.197

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		1.7
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: rs4272; hg19: chr7-92236829;