Variant chr18-54293839-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_007195.3(POLI):c.1595T>C(p.Phe532Ser) variant causes a missense change. The variant allele was found at a frequency of 0.028 in 1,610,050 control chromosomes in the GnomAD database, including 746 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 53 hom., cov: 32)

Exomes 𝑓: 0.029 ( 693 hom. )

Consequence

POLI
NM_007195.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.71

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:

POLI (HGNC:):

POLI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070573986).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3382/152238) while in subpopulation NFE AF= 0.0323 (2196/67974). AF 95% confidence interval is 0.0312. There are 53 homozygotes in gnomad4. There are 1595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLI	NM_007195.3 linkuse as main transcript	c.1595T>C	p.Phe532Ser	missense_variant	10/10	ENST00000579534.6	NP_009126.2	Q9UNA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6 linkuse as main transcript	c.1595T>C	p.Phe532Ser	missense_variant	10/10	1	NM_007195.3	ENSP00000462664.1		Q9UNA4

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3385

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00565

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0413

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0234

AC:

5736

AN:

244740

Hom.:

112

AF XY:

0.0235

AC XY:

3112

AN XY:

132196

show subpopulations

Gnomad AFR exome

AF:

0.00514

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00496

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0334

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0286

AC:

41733

AN:

1457812

Hom.:

693

Cov.:

AF XY:

0.0281

AC XY:

20403

AN XY:

724942

show subpopulations

Gnomad4 AFR exome

AF:

0.00434

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00524

Gnomad4 FIN exome

AF:

0.0384

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0222

AC:

3382

AN:

152238

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1595

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00563

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0413

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0317

Hom.:

190

Bravo

AF:

0.0206

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0338

AC:

291

ExAC

AF:

0.0232

AC:

2810

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

T;T;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;D;D;T

MetaRNN

Benign

0.0071

T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.1

M;.;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.2

.;D;.;.

REVEL

Uncertain

0.52

Sift

Uncertain

0.010

.;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.58

MPC

0.096

ClinPred

0.017

GERP RS

5.5

Varity_R

0.78

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over