rs78996304
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002691.4(POLD1):c.624G>A(p.Pro208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,593,564 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P208P) has been classified as Likely benign.
Frequency
Consequence
NM_002691.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.624G>A | p.Pro208= | synonymous_variant | 6/27 | ENST00000440232.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLD1 | ENST00000440232.7 | c.624G>A | p.Pro208= | synonymous_variant | 6/27 | 1 | NM_002691.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000351 AC: 82AN: 233738Hom.: 0 AF XY: 0.000262 AC XY: 33AN XY: 126106
GnomAD4 exome AF: 0.000130 AC: 188AN: 1441232Hom.: 1 Cov.: 34 AF XY: 0.000111 AC XY: 79AN XY: 714744
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74494
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 2018 | 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. - |
Colorectal cancer, susceptibility to, 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 31, 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 05, 2021 | - - |
Carcinoma of colon Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The POLD1 p.Pro208= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs78996304) “With Likely benign allele” and ClinVar (classified benign by Invitae and Prevention Genetics; and likely benign by GeneDx and Ambry Genetics). The variant was identified in control databases in 88 of 259686 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017), observed in the following populations: African in 1 of 23782 chromosomes (freq: 0.00004), Other in 1 of 6016 chromosomes (freq: 0.0002), European Non-Finnish in 10 of 118560 chromosomes (freq: 0.00008), East Asian in 70 of 18568 chromosomes (freq: 0.004), European Finnish in 5 of 24690 chromosomes (freq: 0.0002), and South Asian in 1 of 27188 chromosomes (freq: 0.00004) while not observed in the Latino and Ashkenazi Jewish. The p.Pro208= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 04, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at