rs3757823

Positions:

• chr7-92674240-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.538-2705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,822 control chromosomes in the GnomAD database, including 6,497 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 0.24 (6497 hom., cov: 31)
• Consequence: CDK6 NM_001145306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK6	NM_001145306.2	c.538-2705T>C		intron_variant		ENST00000424848.3	NP_001138778.1
CDK6	NM_001259.8	c.538-2705T>C		intron_variant			NP_001250.1
CDK6	XM_047419716.1	c.538-2705T>C		intron_variant			XP_047275672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK6	ENST00000424848.3	c.538-2705T>C		intron_variant		1	NM_001145306.2	ENSP00000397087	P1
CDK6	ENST00000265734.8	c.538-2705T>C		intron_variant		1		ENSP00000265734	P1
CDK6	ENST00000473078.1	n.86-2705T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36171 AN: 151704 Hom.: 6470 Cov.: 31

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.239 AC: 36258 AN: 151822 Hom.: 6497 Cov.: 31 AF XY: 0.242 AC XY: 17967 AN XY: 74212

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.228

Alfa AF: 0.139 Hom.: 2124

Bravo AF: 0.249

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.97
DANN	Benign	0.69

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: rs3757823; hg19: chr7-92303554;