chr6-51855874-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_138694.4(PKHD1):c.7911+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00034 in 1,583,284 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_138694.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000427 AC: 65AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000497 AC: 125AN: 251320Hom.: 1 AF XY: 0.000515 AC XY: 70AN XY: 135818
GnomAD4 exome AF: 0.000331 AC: 474AN: 1430962Hom.: 2 Cov.: 26 AF XY: 0.000354 AC XY: 253AN XY: 713826
GnomAD4 genome AF: 0.000427 AC: 65AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74488
ClinVar
Submissions by phenotype
Autosomal recessive polycystic kidney disease Uncertain:1Benign:1
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not specified Benign:1
Variant summary: PKHD1 c.7911+19T>C alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00033 in 1576366 control chromosomes in the gnomAD database, including 2 homozygotes. This frequency is not higher than the maximum estimated for a pathogenic variant in PKHD1 causing Polycystic Kidney And Hepatic Disease (0.0071). The variant, c.7911+19T>C, has been reported in the literature in individuals affected with polycystic kidney disease (e.g. Sharp_2005, Nigro_2023), however, no supportive evidence for causality was provided. These reports do not provide unequivocal conclusions about association of the variant with Polycystic Kidney And Hepatic Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15805161, 37372416). ClinVar contains an entry for this variant (Variation ID: 554778). Based on the evidence outlined above, the variant was classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at