Genetic Variant POLI:c.1067+441C>T (chr18-54284454-C-T) – 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.1067+441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,076 control chromosomes in the GnomAD database, including 5,099 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 0.25 ( 5091 hom., cov: 32)

Exomes 𝑓: 0.40 ( 8 hom. )

Consequence

POLI
NM_007195.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

5 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:

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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=-1.02).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 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	UniProt
POLI	NM_007195.3	MANE Select	c.1067+441C>T	intron	N/A	NP_009126.2	Q9UNA4
POLI	NM_001351632.2		c.992+441C>T	intron	N/A	NP_001338561.1
POLI	NM_001351610.1		c.941+441C>T	intron	N/A	NP_001338539.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLI	ENST00000579534.6	TSL:1 MANE Select	c.1067+441C>T	intron	N/A	ENSP00000462664.1	Q9UNA4
POLI	ENST00000579434.5	TSL:1	c.758+441C>T	intron	N/A	ENSP00000462681.1	J3KSW2
POLI	ENST00000585023.5	TSL:1	n.*162+441C>T	intron	N/A	ENSP00000463971.1	J3QQZ8

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38505

AN:

151832

Hom.:

5092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.0294

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.397

AC:

AN:

126

Hom.:

AF XY:

0.338

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.375

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.422

AC:

AN:

102

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.253

AC:

38512

AN:

151950

Hom.:

5091

Cov.:

AF XY:

0.249

AC XY:

18514

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.236

AC:

9778

AN:

41410

American (AMR)

AF:

0.222

AC:

3388

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3472

East Asian (EAS)

AF:

0.0293

AC:

152

AN:

5188

South Asian (SAS)

AF:

0.248

AC:

1196

AN:

4820

European-Finnish (FIN)

AF:

0.222

AC:

2337

AN:

10550

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19789

AN:

67950

Other (OTH)

AF:

0.259

AC:

547

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1486

2972

4457

5943

7429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.161

Hom.:

331

Bravo

AF:

0.251

Asia WGS

AF:

0.155

AC:

537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

(source)

DANN

Benign

0.54

PhyloP100

-0.0070

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