rs12529717
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_138694.4(PKHD1):c.8302+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,609,690 control chromosomes in the GnomAD database, including 2,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.053 ( 224 hom., cov: 32)
Exomes 𝑓: 0.050 ( 2133 hom. )
Consequence
PKHD1
NM_138694.4 intron
NM_138694.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.627
Genes affected
PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [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=-0.92).
BP6
?
Variant 6-51830843-T-C is Benign according to our data. Variant chr6-51830843-T-C is described in ClinVar as [Benign]. Clinvar id is 96430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.8302+18A>G | intron_variant | ENST00000371117.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.8302+18A>G | intron_variant | 1 | NM_138694.4 | P2 | |||
PKHD1 | ENST00000340994.4 | c.8302+18A>G | intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0529 AC: 8051AN: 152098Hom.: 223 Cov.: 32
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GnomAD3 exomes AF: 0.0522 AC: 13110AN: 251020Hom.: 394 AF XY: 0.0527 AC XY: 7145AN XY: 135676
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GnomAD4 exome AF: 0.0505 AC: 73588AN: 1457474Hom.: 2133 Cov.: 28 AF XY: 0.0513 AC XY: 37231AN XY: 725268
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GnomAD4 genome ? AF: 0.0530 AC: 8070AN: 152216Hom.: 224 Cov.: 32 AF XY: 0.0530 AC XY: 3943AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 04, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive polycystic kidney disease Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 13, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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