dbSNP rs40076: PLK1:c.722+26A>G (chr16-23681084-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Publications

21 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLK1	NM_005030.6 link	c.722+26A>G		intron_variant	Intron 3 of 9	ENST00000300093.9	NP_005021.2	P53350

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLK1	ENST00000300093.9 link	c.722+26A>G		intron_variant	Intron 3 of 9	1	NM_005030.6	ENSP00000300093.4		P53350

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39138

AN:

151932

Hom.:

5205

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.261

AC:

63885

AN:

244810

AF XY:

0.260

show subpopulations

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 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.:

AF XY:

0.239

AC XY:

173093

AN XY:

722808

show subpopulations

African (AFR)

AF:

0.274

AC:

9081

AN:

33092

American (AMR)

AF:

0.260

AC:

11358

AN:

43728

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

5210

AN:

25988

East Asian (EAS)

AF:

0.447

AC:

17495

AN:

39158

South Asian (SAS)

AF:

0.279

AC:

23642

AN:

84812

European-Finnish (FIN)

AF:

0.288

AC:

15360

AN:

53390

Middle Eastern (MID)

AF:

0.230

AC:

1264

AN:

5502

European-Non Finnish (NFE)

AF:

0.223

AC:

246535

AN:

1107314

Other (OTH)

AF:

0.253

AC:

15192

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

13302

26604

39906

53208

66510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.258

AC:

39203

AN:

152050

Hom.:

5217

Cov.:

AF XY:

0.262

AC XY:

19504

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.279

AC:

11581

AN:

41450

American (AMR)

AF:

0.263

AC:

4026

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

705

AN:

3468

East Asian (EAS)

AF:

0.441

AC:

2282

AN:

5172

South Asian (SAS)

AF:

0.296

AC:

1425

AN:

4818

European-Finnish (FIN)

AF:

0.296

AC:

3129

AN:

10568

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.225

AC:

15301

AN:

67972

Other (OTH)

AF:

0.267

AC:

564

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1481

2963

4444

5926

7407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.242

Hom.:

2636

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

(source)

DANN

Benign

0.63

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs40076

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over