chr22-43923801-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000406117.6(PNPLA3):c.-111G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,087,008 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0090 ( 30 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 19 hom. )
Consequence
PNPLA3
ENST00000406117.6 5_prime_UTR, NMD_transcript
ENST00000406117.6 5_prime_UTR, NMD_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.730
Genes affected
PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 22-43923801-G-A is Benign according to our data. Variant chr22-43923801-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 341923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00897 (1365/152244) while in subpopulation AFR AF= 0.0312 (1296/41542). AF 95% confidence interval is 0.0298. There are 30 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA3 | NM_025225.3 | upstream_gene_variant | ENST00000216180.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA3 | ENST00000406117.6 | c.-111G>A | 5_prime_UTR_variant, NMD_transcript_variant | 1/10 | 2 | ||||
PNPLA3 | ENST00000216180.8 | upstream_gene_variant | 1 | NM_025225.3 | P1 | ||||
PNPLA3 | ENST00000423180.2 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00892 AC: 1357AN: 152130Hom.: 30 Cov.: 32
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GnomAD4 exome AF: 0.000962 AC: 899AN: 934764Hom.: 19 Cov.: 12 AF XY: 0.000925 AC XY: 427AN XY: 461756
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GnomAD4 genome AF: 0.00897 AC: 1365AN: 152244Hom.: 30 Cov.: 32 AF XY: 0.00872 AC XY: 649AN XY: 74456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
NAFLD1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at