Variant rs5744761 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_006231.4(POLE):c.1226+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,600,170 control chromosomes in the GnomAD database, including 2,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 547 hom., cov: 32)

Exomes 𝑓: 0.047 ( 2322 hom. )

Consequence

POLE
NM_006231.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.30

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=-0.92).

BP6

Variant 12-132675353-G-A is Benign according to our data. Variant chr12-132675353-G-A is described in ClinVar as [Benign]. Clinvar id is 676492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132675353-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLE	NM_006231.4 linkuse as main transcript	c.1226+45C>T		intron_variant		ENST00000320574.10	NP_006222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10 linkuse as main transcript	c.1226+45C>T		intron_variant		1	NM_006231.4	ENSP00000322570	P1

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10793

AN:

152128

Hom.:

538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0597

GnomAD3 exomes

AF:

0.0609

AC:

14649

AN:

240560

Hom.:

817

AF XY:

0.0538

AC XY:

6993

AN XY:

129870

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00953

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0471

Gnomad OTH exome

AF:

0.0522

GnomAD4 exome

AF:

0.0473

AC:

68506

AN:

1447924

Hom.:

2322

Cov.:

AF XY:

0.0452

AC XY:

32532

AN XY:

719308

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0480

GnomAD4 genome

AF:

0.0711

AC:

10825

AN:

152246

Hom.:

547

Cov.:

AF XY:

0.0716

AC XY:

5327

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0523

Hom.:

150

Bravo

AF:

0.0801

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jun 14, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.045

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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