chr16-23681084-A-G

Variant names:

• chr16-23681084-A-G
• rs40076
• NM_005030.6:c.722+26A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	NM_005030.6	MANE Select	c.722+26A>G		intron	N/A	NP_005021.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK1	ENST00000300093.9	TSL:1 MANE Select	c.722+26A>G		intron	N/A	ENSP00000300093.4
	PLK1	ENST00000885692.1		c.722+26A>G		intron	N/A	ENSP00000555751.1
	PLK1	ENST00000922967.1		c.577+832A>G		intron	N/A	ENSP00000593026.1

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

GnomAD2 exomes AF: 0.261 AC: 63885 AN: 244810 AF XY: 0.260

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.: 31 AF XY: 0.239 AC XY: 173093 AN XY: 722808

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

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

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: 59 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15301 AN: 67972

Other (OTH) AF: 0.267 AC: 564 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
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)

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