12-132624162-T-C

Position:

• chr12-132624162-T-C

Variant summary

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

The NM_006231.4(POLE):​c.*535A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 216,668 control chromosomes in the GnomAD database, including 48,033 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 0.67 (35086 hom., cov: 32)
  • Exomes 𝑓: 0.62 (12947 hom.)
• Consequence: POLE NM_006231.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLE	NM_006231.4	c.*535A>G		3_prime_UTR_variant	49/49	ENST00000320574.10	NP_006222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574	c.*535A>G		3_prime_UTR_variant	49/49	1	NM_006231.4	ENSP00000322570.5

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101923 AN: 151854 Hom.: 35053 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.622 AC: 40263 AN: 64696 Hom.: 12947 Cov.: 0 AF XY: 0.621 AC XY: 18740 AN XY: 30164

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.733

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.671 AC: 102009 AN: 151972 Hom.: 35086 Cov.: 32 AF XY: 0.673 AC XY: 49957 AN XY: 74274

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.649

Alfa AF: 0.602 Hom.: 26336

Bravo AF: 0.688

Asia WGS AF: 0.706 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.57
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs14302; hg19: chr12-133200748;