rs20582
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002691.4(POLD1):c.324G>A(p.Ala108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,611,890 control chromosomes in the GnomAD database, including 9,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A108A) has been classified as Likely benign.
Frequency
Consequence
NM_002691.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.324G>A | p.Ala108= | synonymous_variant | 4/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.324G>A | p.Ala108= | synonymous_variant | 4/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.139 AC: 21097AN: 151992Hom.: 2207 Cov.: 32
GnomAD3 exomes AF: 0.111 AC: 27177AN: 245174Hom.: 2083 AF XY: 0.113 AC XY: 15043AN XY: 133638
GnomAD4 exome AF: 0.0869 AC: 126900AN: 1459780Hom.: 7425 Cov.: 34 AF XY: 0.0901 AC XY: 65460AN XY: 726348
GnomAD4 genome AF: 0.139 AC: 21131AN: 152110Hom.: 2213 Cov.: 32 AF XY: 0.138 AC XY: 10251AN XY: 74382
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 16, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 02, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. - |
Colorectal cancer, susceptibility to, 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Mandibular hypoplasia-deafness-progeroid syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 17, 2016 | Variant summary: The POLD1 c.324G>A (p.Ala108Ala) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing, however, these predictions have yet to be functionally assessed. This variant was observed in the large, broad control population, ExAC, with an allele frequency of 13554/117858 (1121 homozygotes, 1/8, frequency: 0.1150028), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic POLD1 variant of 1/70422 (0.0000142), suggesting this variant is likely a benign polymorphism. Therefore, the variant of interest is classified as Benign. - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at