rs746459362
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The ENST00000320574.10(POLE):c.6657+7C>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 0.0000143 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
ENST00000320574.10 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLE | NM_006231.4 | c.6657+7C>T | splice_region_variant, intron_variant | ENST00000320574.10 | NP_006222.2 | |||
POLE | XM_011534795.4 | c.6657+7C>T | splice_region_variant, intron_variant | XP_011533097.1 | ||||
POLE | XM_011534797.4 | c.5736+7C>T | splice_region_variant, intron_variant | XP_011533099.1 | ||||
POLE | XM_011534802.4 | c.3645+7C>T | splice_region_variant, intron_variant | XP_011533104.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLE | ENST00000320574.10 | c.6657+7C>T | splice_region_variant, intron_variant | 1 | NM_006231.4 | ENSP00000322570 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250544Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135460
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460834Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 726734
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74344
ClinVar
Submissions by phenotype
POLE-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 28, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at