chr16-2089712-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001009944.3(PKD1):c.*15G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,566,408 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 18 hom., cov: 34)
Exomes 𝑓: 0.012 ( 174 hom. )
Consequence
PKD1
NM_001009944.3 3_prime_UTR
NM_001009944.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.541
Genes affected
PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 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=-0.87).
BP6
?
Variant 16-2089712-C-T is Benign according to our data. Variant chr16-2089712-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 256884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2089712-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0123 (1875/152364) while in subpopulation AMR AF= 0.0188 (288/15304). AF 95% confidence interval is 0.017. There are 18 homozygotes in gnomad4. There are 1049 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1875 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.*15G>A | 3_prime_UTR_variant | 46/46 | ENST00000262304.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.*15G>A | 3_prime_UTR_variant | 46/46 | 1 | NM_001009944.3 | P5 | ||
PKD1 | ENST00000423118.5 | c.*15G>A | 3_prime_UTR_variant | 46/46 | 1 | A2 | |||
PKD1 | ENST00000472577.1 | n.955G>A | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0123 AC: 1875AN: 152246Hom.: 18 Cov.: 34
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GnomAD3 exomes AF: 0.0144 AC: 2495AN: 173144Hom.: 41 AF XY: 0.0135 AC XY: 1267AN XY: 93736
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GnomAD4 exome AF: 0.0124 AC: 17521AN: 1414044Hom.: 174 Cov.: 31 AF XY: 0.0121 AC XY: 8442AN XY: 698910
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Polycystic kidney disease, adult type Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 13, 2020 | - - |
Autosomal dominant polycystic kidney disease Benign:1
Likely benign, criteria provided, single submitter | research | Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research | Jan 01, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at