rs149096523
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_002691.4(POLD1):c.714G>A(p.Thr238Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,610,868 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 (★★).
Frequency
Consequence
NM_002691.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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POLD1 | NM_002691.4 | c.714G>A | p.Thr238Thr | synonymous_variant | Exon 6 of 27 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152260Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000207 AC: 51AN: 246412Hom.: 0 AF XY: 0.000187 AC XY: 25AN XY: 133582
GnomAD4 exome AF: 0.000420 AC: 613AN: 1458490Hom.: 1 Cov.: 34 AF XY: 0.000389 AC XY: 282AN XY: 725046
GnomAD4 genome AF: 0.000289 AC: 44AN: 152378Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24AN XY: 74516
ClinVar
Submissions by phenotype
not provided Benign:5
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POLD1: BP4, BP7 -
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not specified Benign:4
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Colorectal cancer, susceptibility to, 10 Benign:3
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Hereditary cancer-predisposing syndrome Benign:3
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. -
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BA1, BP4, BP7 c.714G>A, located in exon 6 of the POLD1 gene, is predicted to result in no amino acid change, p.(Thr238=) (BP7). This variant is found in 56/264174 alleles at a frequency of 0.02% in the gnomAD v2.1.1 database, non-cancer dataset (BA1). The SpliceAI algorithm predicts no significant impact on splicing (BP4). To our knowledge, neither relevant clinical data nor well-established functional studies have been reported for this variant. This variant has been reported in the ClinVar database (9x benign, 3x likely benign) and in LOVD (2x likely benign). Based on currently available information, the variant c.714G>A should be considered a likely benign variant, according to ACMG/AMP classification guidelines. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at