rs7963858

Positions:

• chr12-132630062-T-C
• chr12-132630062-T-G

Variant summary

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

The NM_006231.4(POLE):​c.6330+2253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,108 control chromosomes in the GnomAD database, including 35,107 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 0.68 (35107 hom., cov: 33)
• Consequence: POLE NM_006231.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLE	NM_006231.4	c.6330+2253A>G		intron_variant		ENST00000320574.10	NP_006222.2
POLE	XM_011534795.4	c.6330+2253A>G		intron_variant			XP_011533097.1
POLE	XM_011534797.4	c.5409+2253A>G		intron_variant			XP_011533099.1
POLE	XM_011534802.4	c.3318+2253A>G		intron_variant			XP_011533104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10	c.6330+2253A>G		intron_variant		1	NM_006231.4	ENSP00000322570	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103014 AN: 151988 Hom.: 35084 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.678 AC: 103081 AN: 152108 Hom.: 35107 Cov.: 33 AF XY: 0.679 AC XY: 50497 AN XY: 74346

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.680

Alfa AF: 0.673 Hom.: 32863

Bravo AF: 0.688

Asia WGS AF: 0.724 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.22
DANN	Benign	0.22

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: rs7963858; hg19: chr12-133206648;