12-132632296-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006231.4(POLE):c.6330+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,600,686 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

POLE
NM_006231.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.85

Variant links:

Genes affected

POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]

POLE 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 (BayesDel_noAF=-0.93).

BP6

Variant 12-132632296-C-T is Benign according to our data. Variant chr12-132632296-C-T is described in ClinVar as [Benign]. Clinvar id is 380224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132632296-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1796/152144) while in subpopulation AFR AF= 0.0413 (1714/41480). AF 95% confidence interval is 0.0397. There are 25 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
POLE	NM_006231.4 link	c.6330+19G>A	intron_variant	Intron 45 of 48	ENST00000320574.10	NP_006222.2	Q07864
POLE	XM_011534795.4 link	c.6330+19G>A	intron_variant	Intron 45 of 47		XP_011533097.1
POLE	XM_011534797.4 link	c.5409+19G>A	intron_variant	Intron 37 of 39		XP_011533099.1
POLE	XM_011534802.4 link	c.3318+19G>A	intron_variant	Intron 21 of 23		XP_011533104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10 link	c.6330+19G>A		intron_variant	Intron 45 of 48	1	NM_006231.4	ENSP00000322570.5		Q07864

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1795

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00816

GnomAD3 exomes

AF:

0.00318

AC:

793

AN:

249172

Hom.:

AF XY:

0.00227

AC XY:

306

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.000987

GnomAD4 exome

AF:

0.00117

AC:

1702

AN:

1448542

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

733

AN XY:

721464

show subpopulations

Gnomad4 AFR exome

AF:

0.0421

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000815

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000282

Gnomad4 OTH exome

AF:

0.00251

GnomAD4 genome

AF:

0.0118

AC:

1796

AN:

152144

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

857

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 17, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 06, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Apr 17, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Colorectal cancer, susceptibility to, 12

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.095

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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