Variant rs8305 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007195.3(POLI):c.2191G>A(p.Ala731Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,607,918 control chromosomes in the GnomAD database, including 412,972 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.77 ( 46386 hom., cov: 32)

Exomes 𝑓: 0.71 ( 366586 hom. )

Consequence

POLI
NM_007195.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.631

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.975265E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLI	NM_007195.3 linkuse as main transcript	c.2191G>A	p.Ala731Thr	missense_variant	10/10	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6 linkuse as main transcript	c.2191G>A	p.Ala731Thr	missense_variant	10/10	1	NM_007195.3	ENSP00000462664	P1

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117549

AN:

151988

Hom.:

46335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.943

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.686

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.720

AC:

176904

AN:

245858

Hom.:

64556

AF XY:

0.721

AC XY:

95905

AN XY:

133008

show subpopulations

Gnomad AFR exome

AF:

0.947

Gnomad AMR exome

AF:

0.602

Gnomad ASJ exome

AF:

0.805

Gnomad EAS exome

AF:

0.720

Gnomad SAS exome

AF:

0.769

Gnomad FIN exome

AF:

0.719

Gnomad NFE exome

AF:

0.702

Gnomad OTH exome

AF:

0.710

GnomAD4 exome

AF:

0.707

AC:

1029985

AN:

1455812

Hom.:

366586

Cov.:

AF XY:

0.709

AC XY:

513453

AN XY:

723990

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.612

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.734

Gnomad4 SAS exome

AF:

0.766

Gnomad4 FIN exome

AF:

0.717

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.731

GnomAD4 genome

AF:

0.773

AC:

117645

AN:

152106

Hom.:

46386

Cov.:

AF XY:

0.774

AC XY:

57549

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.943

Gnomad4 AMR

AF:

0.684

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.713

Gnomad4 SAS

AF:

0.775

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.764

Alfa

AF:

0.711

Hom.:

92487

Bravo

AF:

0.773

TwinsUK

AF:

0.691

AC:

2563

ALSPAC

AF:

0.690

AC:

2660

ESP6500AA

AF:

0.932

AC:

4108

ESP6500EA

AF:

0.699

AC:

6008

ExAC

AF:

0.726

AC:

88161

Asia WGS

AF:

0.755

AC:

2628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.034

DANN

Benign

0.57

DEOGEN2

Benign

0.025

T;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.094

T;T;T;T

MetaRNN

Benign

6.0e-7

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.42

.;N;.;.

REVEL

Benign

0.030

Sift

Benign

0.89

.;T;.;.

Sift4G

Benign

0.79

T;T;T;T

Polyphen

0.0010

B;.;.;.

Vest4

0.033

MPC

0.013

ClinPred

0.0025

GERP RS

-5.2

Varity_R

0.016

gMVP

0.11

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

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