Variant rs3730477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174084.2(POLL):c.1312C>T(p.Arg438Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,192 control chromosomes in the GnomAD database, including 33,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2392 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31057 hom. )

Consequence

POLL
NM_001174084.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]

POLL links:

POLL (HGNC:):

POLL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017029941).

BP6

Variant 10-101580299-G-A is Benign according to our data. Variant chr10-101580299-G-A is described in ClinVar as [Benign]. Clinvar id is 1248188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLL	NM_001174084.2 linkuse as main transcript	c.1312C>T	p.Arg438Trp	missense_variant	8/9	ENST00000370162.8	NP_001167555.1	Q9UGP5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLL	ENST00000370162.8 linkuse as main transcript	c.1312C>T	p.Arg438Trp	missense_variant	8/9	1	NM_001174084.2	ENSP00000359181.3		Q9UGP5-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24444

AN:

152030

Hom.:

2393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.168

AC:

42107

AN:

251244

Hom.:

4191

AF XY:

0.171

AC XY:

23283

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0330

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.200

AC:

292446

AN:

1461044

Hom.:

31057

Cov.:

AF XY:

0.199

AC XY:

144760

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.161

AC:

24434

AN:

152148

Hom.:

2392

Cov.:

AF XY:

0.158

AC XY:

11723

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.0360

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.209

Hom.:

8454

Bravo

AF:

0.156

TwinsUK

AF:

0.216

AC:

801

ALSPAC

AF:

0.208

AC:

803

ESP6500AA

AF:

0.0742

AC:

327

ESP6500EA

AF:

0.228

AC:

1964

ExAC

AF:

0.168

AC:

20336

Asia WGS

AF:

0.0620

AC:

215

AN:

3478

EpiCase

AF:

0.231

EpiControl

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 19806195, 20693240) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;T;.;T;T;.;T;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;.;T;.;D;T;D;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;M;.;M;.;.;M;.;.

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.8

D;D;D;D;D;.;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.016

D;D;D;D;D;.;D;T;D

Sift4G

Uncertain

0.034

D;D;D;D;D;D;D;.;D

Polyphen

1.0

D;D;D;D;.;.;D;.;.

Vest4

0.13

MPC

0.18

ClinPred

0.042

GERP RS

1.7

Varity_R

0.28

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over