rs27770

Positions:

• chr16-23690217-A-G
• chr16-23690217-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000300093.9(PLK1):​c.*154A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 649,526 control chromosomes in the GnomAD database, including 17,202 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 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.23 (13969 hom.)
• Consequence: PLK1 ENST00000300093.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK1	NM_005030.6	c.*154A>G		3_prime_UTR_variant	10/10	ENST00000300093.9	NP_005021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLK1	ENST00000300093.9	c.*154A>G		3_prime_UTR_variant	10/10	1	NM_005030.6	ENSP00000300093	P1
PLK1	ENST00000562272.5	n.3986A>G		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29877 AN: 151972 Hom.: 3236 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.232 AC: 24425 AN: 105350 Hom.: 3074 AF XY: 0.234 AC XY: 13102 AN XY: 55992

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.226 AC: 112483 AN: 497436 Hom.: 13969 Cov.: 5 AF XY: 0.228 AC XY: 60190 AN XY: 264204

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.197 AC: 29888 AN: 152090 Hom.: 3233 Cov.: 32 AF XY: 0.200 AC XY: 14902 AN XY: 74346

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.211

Alfa AF: 0.194 Hom.: 646

Bravo AF: 0.187

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs27770; hg19: chr16-23701538;