Genetic Variant POLI:c.1068-117A>G (chr18-54287164-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_007195.3(POLI):c.1068-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 624,068 control chromosomes in the GnomAD database, including 1,392 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 0.069 ( 430 hom., cov: 32)

Exomes 𝑓: 0.058 ( 962 hom. )

Consequence

POLI
NM_007195.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.496

Publications

4 publications found

Variant links:

Genes affected

POLI (HGNC:9182): (DNA polymerase iota) The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion. [provided by RefSeq, May 2017]

POLI 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007195.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLI	NM_007195.3	MANE Select	c.1068-117A>G	intron	N/A	NP_009126.2
POLI	NM_001351632.2		c.993-117A>G	intron	N/A	NP_001338561.1
POLI	NM_001351610.1		c.942-117A>G	intron	N/A	NP_001338539.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLI	ENST00000579534.6	TSL:1 MANE Select	c.1068-117A>G	intron	N/A	ENSP00000462664.1
POLI	ENST00000579434.5	TSL:1	c.759-117A>G	intron	N/A	ENSP00000462681.1
POLI	ENST00000585023.5	TSL:1	n.*163-117A>G	intron	N/A	ENSP00000463971.1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10508

AN:

152124

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.0685

Gnomad EAS

AF:

0.00481

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0685

Gnomad OTH

AF:

0.0751

GnomAD4 exome

AF:

0.0583

AC:

27485

AN:

471824

Hom.:

962

AF XY:

0.0563

AC XY:

13972

AN XY:

248110

show subpopulations

African (AFR)

AF:

0.0904

AC:

1131

AN:

12512

American (AMR)

AF:

0.0423

AC:

827

AN:

19542

Ashkenazi Jewish (ASJ)

AF:

0.0684

AC:

888

AN:

12990

East Asian (EAS)

AF:

0.00416

AC:

118

AN:

28372

South Asian (SAS)

AF:

0.0288

AC:

1260

AN:

43738

European-Finnish (FIN)

AF:

0.0676

AC:

2237

AN:

33094

Middle Eastern (MID)

AF:

0.0356

AC:

AN:

2162

European-Non Finnish (NFE)

AF:

0.0662

AC:

19455

AN:

294028

Other (OTH)

AF:

0.0588

AC:

1492

AN:

25386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1202

2404

3605

4807

6009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

246

492

738

984

1230

<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:

0.0691

AC:

10526

AN:

152244

Hom.:

430

Cov.:

AF XY:

0.0687

AC XY:

5114

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0881

AC:

3658

AN:

41536

American (AMR)

AF:

0.0529

AC:

808

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0685

AC:

238

AN:

3472

East Asian (EAS)

AF:

0.00482

AC:

AN:

5184

South Asian (SAS)

AF:

0.0282

AC:

136

AN:

4828

European-Finnish (FIN)

AF:

0.0676

AC:

717

AN:

10614

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0685

AC:

4657

AN:

68006

Other (OTH)

AF:

0.0758

AC:

160

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

479

957

1436

1914

2393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0271

Hom.:

Bravo

AF:

0.0702

Asia WGS

AF:

0.0340

AC:

117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.56

(source)

DANN

Benign

0.48

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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