rs139836643
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006231.4(POLE):c.1360-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,574,938 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006231.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- POLE-related polyposis and colorectal cancer syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- colorectal cancer, susceptibility to, 12Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
- facial dysmorphism-immunodeficiency-livedo-short stature syndromeInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
- intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiencyInheritance: AR Classification: STRONG Submitted by: G2P
- IMAGe syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Polymerase proofreading-related adenomatous polyposisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000939 AC: 143AN: 152240Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000282 AC: 71AN: 251338 AF XY: 0.000265 show subpopulations
GnomAD4 exome AF: 0.000163 AC: 232AN: 1422580Hom.: 3 Cov.: 26 AF XY: 0.000180 AC XY: 128AN XY: 710198 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000945 AC: 144AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000805 AC XY: 60AN XY: 74510 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:7
- -
- -
- -
POLE: BP4, BS1 -
- -
- -
- -
Colorectal cancer, susceptibility to, 12 Benign:2
This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -
- -
not specified Benign:1
- -
Polymerase proofreading-related adenomatous polyposis;C3896578:Familial colorectal cancer type X Benign:1
- -
Hereditary cancer-predisposing syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at