rs140216790
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_002691.4(POLD1):c.1620C>T(p.Gly540=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,324 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00091 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0014 ( 3 hom. )
Consequence
POLD1
NM_002691.4 synonymous
NM_002691.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.43
Genes affected
POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 19-50407108-C-T is Benign according to our data. Variant chr19-50407108-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 220890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50407108-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.43 with no splicing effect.
BS2
High AC in GnomAd4 at 138 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.1620C>T | p.Gly540= | synonymous_variant | 13/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.1620C>T | p.Gly540= | synonymous_variant | 13/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000907 AC: 138AN: 152136Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000857 AC: 214AN: 249844Hom.: 1 AF XY: 0.000732 AC XY: 99AN XY: 135186
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GnomAD4 exome AF: 0.00141 AC: 2063AN: 1461070Hom.: 3 Cov.: 34 AF XY: 0.00133 AC XY: 970AN XY: 726898
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GnomAD4 genome AF: 0.000906 AC: 138AN: 152254Hom.: 0 Cov.: 31 AF XY: 0.000927 AC XY: 69AN XY: 74440
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:17
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:8
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 23, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 04, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | POLD1: BP4, BP7, BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 31, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2017 | - - |
Colorectal cancer, susceptibility to, 10 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 17, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Oct 25, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 04, 2015 | This alteration is classified as likely 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at