rs4883582

Positions:

• chr12-132666147-C-A
• chr12-132666147-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006231.4(POLE):​c.2320-697G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,150 control chromosomes in the GnomAD database, including 1,399 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1399 hom., cov: 33)
• Consequence: POLE NM_006231.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLE	NM_006231.4	c.2320-697G>T		intron_variant		ENST00000320574.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLE	ENST00000320574.10	c.2320-697G>T		intron_variant		1	NM_006231.4	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19393 AN: 152032 Hom.: 1398 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19404 AN: 152150 Hom.: 1399 Cov.: 33 AF XY: 0.123 AC XY: 9133 AN XY: 74366

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0340

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.137

Alfa AF: 0.126 Hom.: 1219

Bravo AF: 0.134

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs4883582; hg19: chr12-133242733;