12-132661167-G-GAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1

The NM_006231.4(POLE):​c.2865-5_2865-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000903 in 1,368,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00098 ( 0 hom. )

Consequence

POLE
NM_006231.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.191
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6
Variant 12-132661167-G-GAA is Benign according to our data. Variant chr12-132661167-G-GAA is described in ClinVar as [Likely_benign]. Clinvar id is 801260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000985 (1215/1233756) while in subpopulation SAS AF= 0.0027 (185/68468). AF 95% confidence interval is 0.00238. There are 0 homozygotes in gnomad4_exome. There are 638 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POLENM_006231.4 linkc.2865-5_2865-4dupTT splice_region_variant, intron_variant ENST00000320574.10 NP_006222.2 Q07864

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POLEENST00000320574.10 linkc.2865-5_2865-4dupTT splice_region_variant, intron_variant 1 NM_006231.4 ENSP00000322570.5 Q07864

Frequencies

GnomAD3 genomes
AF:
0.000156
AC:
21
AN:
134284
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000129
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000178
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000985
AC:
1215
AN:
1233756
Hom.:
0
Cov.:
0
AF XY:
0.00104
AC XY:
638
AN XY:
612260
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
Gnomad4 AMR exome
AF:
0.00168
Gnomad4 ASJ exome
AF:
0.00180
Gnomad4 EAS exome
AF:
0.00113
Gnomad4 SAS exome
AF:
0.00270
Gnomad4 FIN exome
AF:
0.00109
Gnomad4 NFE exome
AF:
0.000783
Gnomad4 OTH exome
AF:
0.00115
GnomAD4 genome
AF:
0.000156
AC:
21
AN:
134284
Hom.:
0
Cov.:
31
AF XY:
0.000139
AC XY:
9
AN XY:
64610
show subpopulations
Gnomad4 AFR
AF:
0.000249
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000129
Gnomad4 NFE
AF:
0.000178
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingCenter for Genomic Medicine, Rigshospitalet, Copenhagen University HospitalAug 15, 2023- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingQuest Diagnostics Nichols Institute San Juan CapistranoMar 11, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs369732588; hg19: chr12-133237753; API