rs56022846
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002691.4(POLD1):c.971-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,552,782 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 0.00091 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
POLD1
NM_002691.4 intron
NM_002691.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.906
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 19-50403034-G-A is Benign according to our data. Variant chr19-50403034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 246155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50403034-G-A is described in Lovd as [Benign].
BS2
?
High AC in GnomAd4 at 139 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.971-19G>A | intron_variant | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.971-19G>A | intron_variant | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000913 AC: 139AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000238 AC: 37AN: 155546Hom.: 0 AF XY: 0.000206 AC XY: 17AN XY: 82462
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GnomAD4 exome AF: 0.000116 AC: 162AN: 1400474Hom.: 0 Cov.: 32 AF XY: 0.0000955 AC XY: 66AN XY: 691076
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GnomAD4 genome ? AF: 0.000913 AC: 139AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000846 AC XY: 63AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Colorectal cancer, susceptibility to, 10 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Aug 22, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 19, 2023 | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2017 | 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:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 09, 2016 | - - |
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