rs40076

Positions:

• chr16-23681084-A-G
• chr16-23681084-A-T

Variant summary

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

The NM_005030.6(PLK1):​c.722+26A>G 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 1,605,048 control chromosomes in the GnomAD database, including 47,965 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 0.26 (5217 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42748 hom.)
• Consequence: PLK1 NM_005030.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

Genes affected

PLK1 (HGNC:9077): (polo like kinase 1) The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy. [provided by RefSeq, Sep 2015]

PLK1 (HGNC:):

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 = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK1	NM_005030.6	c.722+26A>G		intron_variant		ENST00000300093.9	NP_005021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLK1	ENST00000300093.9	c.722+26A>G		intron_variant		1	NM_005030.6	ENSP00000300093.4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39138 AN: 151932 Hom.: 5205 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.261 AC: 63885 AN: 244810 Hom.: 8896 AF XY: 0.260 AC XY: 34407 AN XY: 132412

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.238 AC: 345137 AN: 1452998 Hom.: 42748 Cov.: 31 AF XY: 0.239 AC XY: 173093 AN XY: 722808

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.258 AC: 39203 AN: 152050 Hom.: 5217 Cov.: 32 AF XY: 0.262 AC XY: 19504 AN XY: 74322

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.267

Alfa AF: 0.231 Hom.: 1106

Bravo AF: 0.255

Asia WGS AF: 0.352 AC: 1223 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	5.3
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs40076; hg19: chr16-23692405; COSMIC: COSV55620678; COSMIC: COSV55620678;