rs142575178
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001009944.3(PKD1):c.4872C>T(p.Ile1624Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.000367 in 1,612,654 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_001009944.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.4872C>T | p.Ile1624Ile | synonymous_variant | Exon 15 of 46 | ENST00000262304.9 | NP_001009944.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00189 AC: 288AN: 152238Hom.: 2 Cov.: 34
GnomAD3 exomes AF: 0.000526 AC: 131AN: 249190Hom.: 1 AF XY: 0.000450 AC XY: 61AN XY: 135408
GnomAD4 exome AF: 0.000208 AC: 304AN: 1460298Hom.: 1 Cov.: 36 AF XY: 0.000176 AC XY: 128AN XY: 726438
GnomAD4 genome AF: 0.00189 AC: 288AN: 152356Hom.: 2 Cov.: 34 AF XY: 0.00170 AC XY: 127AN XY: 74498
ClinVar
Submissions by phenotype
not specified Benign:1
- -
Polycystic kidney disease Benign:1
The PKD1 p.Ile1624Ile variant was not identified in the literature nor was it identified in the Clinvitae, ClinVar, GeneInsight COGR, MutDB, PKD1-LOVD and PKD1-LOVD 3.0 databases nor was it identified in the NHLBI GO Exome Sequencing Project. The variant was identified in the ADPKD Mutation Database as likely neutral. The variant was also identified in dbSNP (ID: rs142575178) as “NA”, in the 1000 Genomes Project in 14 of 500 chromosomes (frequency: 0.028), in the Exome Aggregation Consortium database (August 8, 2016) in 77 of 118592 chromosomes (frequency: 0.0006) in the following populations: African in 76 of 9904 chromosomes (frequency: 0.008) and European (Non-Finnish) in 1 of 61652 chromosomes (frequency: 0.00002), but was not seen in East Asian, European (Finnish), Latino and South Asian populations. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Ile1624Ile variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -
PKD1-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at