NM_006231.4:c.6330+15G>A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006231.4(POLE):c.6330+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,601,652 control chromosomes in the GnomAD database, including 170,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006231.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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POLE | NM_006231.4 | c.6330+15G>A | intron_variant | Intron 45 of 48 | ENST00000320574.10 | NP_006222.2 | ||
POLE | XM_011534795.4 | c.6330+15G>A | intron_variant | Intron 45 of 47 | XP_011533097.1 | |||
POLE | XM_011534797.4 | c.5409+15G>A | intron_variant | Intron 37 of 39 | XP_011533099.1 | |||
POLE | XM_011534802.4 | c.3318+15G>A | intron_variant | Intron 21 of 23 | XP_011533104.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.500 AC: 75845AN: 151806Hom.: 19538 Cov.: 32
GnomAD3 exomes AF: 0.494 AC: 122871AN: 248930Hom.: 31412 AF XY: 0.489 AC XY: 65764AN XY: 134544
GnomAD4 exome AF: 0.452 AC: 654914AN: 1449730Hom.: 151158 Cov.: 30 AF XY: 0.454 AC XY: 327967AN XY: 721740
GnomAD4 genome AF: 0.500 AC: 75892AN: 151922Hom.: 19553 Cov.: 32 AF XY: 0.502 AC XY: 37291AN XY: 74268
ClinVar
Submissions by phenotype
not specified Benign:5
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Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:4
Variant summary: c.6330+15G>A in POLE gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 49% (58808/119032 chrs tested), including numerous homozygous occurrences. The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.0014%, suggesting that it is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals or cited by reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -
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Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency Benign:1
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Colorectal cancer, susceptibility to, 12 Benign:1
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Facial dysmorphism-immunodeficiency-livedo-short stature syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at