rs201418203
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_020376.4(PNPLA2):c.487-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 1,612,576 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020376.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA2 | NM_020376.4 | c.487-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000336615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA2 | ENST00000336615.9 | c.487-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_020376.4 | P1 | |||
PNPLA2 | ENST00000531923.1 | n.374C>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
PNPLA2 | ENST00000525250.5 | n.1093-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152198Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000856 AC: 215AN: 251080Hom.: 2 AF XY: 0.000898 AC XY: 122AN XY: 135802
GnomAD4 exome AF: 0.000612 AC: 893AN: 1460260Hom.: 5 Cov.: 31 AF XY: 0.000657 AC XY: 477AN XY: 726540
GnomAD4 genome ? AF: 0.000538 AC: 82AN: 152316Hom.: 1 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74484
ClinVar
Submissions by phenotype
Neutral lipid storage myopathy Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at