chr19-50398839-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002691.4(POLD1):c.-1-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,607,370 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 Uncertain significance (no stars).
Frequency
Consequence
NM_002691.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLD1 | NM_002691.4 | c.-1-12C>T | intron_variant | Intron 1 of 26 | ENST00000440232.7 | NP_002682.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000423 AC: 1AN: 236540Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128680
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1455134Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 723426
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Carcinoma of colon Uncertain:1
The POLD1 c.-4-9C>T variant was not identified in the literature nor was it identified in the ClinVar database. The variant was identified in dbSNP (rs778338383) as “NA”. The variant was identified in control databases in 1 of 236,540 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 1 of 106,394 chromosomes (freq: 0.000009), but it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, Finnish, Other or South Asian populations. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at