Genetic Variant NM_016218.6:c.1356+119G>A (chr5-75590559-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016218.6(POLK):c.1356+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 663,376 control chromosomes in the GnomAD database, including 3,105 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 0.078 ( 555 hom., cov: 32)

Exomes 𝑓: 0.092 ( 2550 hom. )

Consequence

POLK
NM_016218.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

7 publications found

Variant links:

Genes affected

POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

POLK 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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016218.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLK	NM_016218.6	MANE Select	c.1356+119G>A	intron	N/A	NP_057302.1
POLK	NM_001387111.3		c.1398+119G>A	intron	N/A	NP_001374040.1
POLK	NM_001395894.1		c.1398+119G>A	intron	N/A	NP_001382823.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLK	ENST00000241436.9	TSL:1 MANE Select	c.1356+119G>A	intron	N/A	ENSP00000241436.4
POLK	ENST00000508526.5	TSL:1	c.935-5663G>A	intron	N/A	ENSP00000426853.1
POLK	ENST00000504026.5	TSL:1	c.1356+119G>A	intron	N/A	ENSP00000425075.1

Frequencies

GnomAD3 genomes

AF:

0.0781

AC:

11879

AN:

152084

Hom.:

551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0603

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0684

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0703

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0678

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0835

Gnomad OTH

AF:

0.0888

GnomAD4 exome

AF:

0.0921

AC:

47076

AN:

511174

Hom.:

2550

Cov.:

AF XY:

0.0971

AC XY:

26645

AN XY:

274412

show subpopulations

African (AFR)

AF:

0.0601

AC:

844

AN:

14042

American (AMR)

AF:

0.0502

AC:

1376

AN:

27402

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

2651

AN:

16338

East Asian (EAS)

AF:

0.0766

AC:

2460

AN:

32134

South Asian (SAS)

AF:

0.164

AC:

8734

AN:

53270

European-Finnish (FIN)

AF:

0.0663

AC:

2351

AN:

35478

Middle Eastern (MID)

AF:

0.153

AC:

327

AN:

2142

European-Non Finnish (NFE)

AF:

0.0853

AC:

25763

AN:

302018

Other (OTH)

AF:

0.0907

AC:

2570

AN:

28350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2107

4214

6322

8429

10536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0782

AC:

11895

AN:

152202

Hom.:

555

Cov.:

AF XY:

0.0797

AC XY:

5932

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0604

AC:

2510

AN:

41552

American (AMR)

AF:

0.0683

AC:

1044

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

530

AN:

3472

East Asian (EAS)

AF:

0.0701

AC:

364

AN:

5192

South Asian (SAS)

AF:

0.169

AC:

816

AN:

4828

European-Finnish (FIN)

AF:

0.0678

AC:

718

AN:

10586

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0835

AC:

5674

AN:

67968

Other (OTH)

AF:

0.0870

AC:

184

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

561

1123

1684

2246

2807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0817

Hom.:

181

Bravo

AF:

0.0748

Asia WGS

AF:

0.118

AC:

408

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.3

(source)

DANN

Benign

0.54

PhyloP100

-0.0090

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over