rs116414807
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_138694.4(PKHD1):c.391-43T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,451,414 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0086 ( 26 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 16 hom. )
Consequence
PKHD1
NM_138694.4 intron
NM_138694.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.267
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=-0.85).
BP6
Variant 6-52076376-A-T is Benign according to our data. Variant chr6-52076376-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 262402.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 = 0.00859 (1309/152354) while in subpopulation AFR AF= 0.0288 (1197/41574). AF 95% confidence interval is 0.0274. There are 26 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKHD1 | NM_138694.4 | c.391-43T>A | intron_variant | ENST00000371117.8 | NP_619639.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKHD1 | ENST00000371117.8 | c.391-43T>A | intron_variant | 1 | NM_138694.4 | ENSP00000360158.3 | ||||
PKHD1 | ENST00000340994.4 | c.391-43T>A | intron_variant | 5 | ENSP00000341097.4 |
Frequencies
GnomAD3 genomes AF: 0.00861 AC: 1310AN: 152236Hom.: 26 Cov.: 33
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GnomAD3 exomes AF: 0.00241 AC: 603AN: 250190Hom.: 11 AF XY: 0.00173 AC XY: 234AN XY: 135272
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GnomAD4 exome AF: 0.00103 AC: 1340AN: 1299060Hom.: 16 Cov.: 20 AF XY: 0.000922 AC XY: 604AN XY: 655214
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GnomAD4 genome AF: 0.00859 AC: 1309AN: 152354Hom.: 26 Cov.: 33 AF XY: 0.00768 AC XY: 572AN XY: 74502
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ClinVar
Significance: Benign/Likely 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 01, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Autosomal recessive polycystic kidney disease Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 13, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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