chr19-50402227-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000440232.7(POLD1):c.612C>T(p.His204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,586,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
POLD1
ENST00000440232.7 synonymous
ENST00000440232.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.795
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 19-50402227-C-T is Benign according to our data. Variant chr19-50402227-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.795 with no splicing effect.
BS2
High AC in GnomAd4 at 112 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.612C>T | p.His204= | synonymous_variant | 6/27 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.612C>T | p.His204= | synonymous_variant | 6/27 | 1 | NM_002691.4 | ENSP00000406046 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000729 AC: 111AN: 152250Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000153 AC: 35AN: 228340Hom.: 0 AF XY: 0.000155 AC XY: 19AN XY: 122802
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GnomAD4 exome AF: 0.0000934 AC: 134AN: 1434596Hom.: 0 Cov.: 34 AF XY: 0.0000788 AC XY: 56AN XY: 710584
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GnomAD4 genome AF: 0.000735 AC: 112AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74506
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
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 | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 13, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 04, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 23, 2018 | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 22, 2024 | See Variant Classification Assertion Criteria. - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 09, 2018 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 18, 2021 | - - |
Colorectal cancer, susceptibility to, 10 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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