17-46030522-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_015443.4(KANSL1):c.*954C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 150,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0038 ( 0 hom., cov: 31)
Exomes 𝑓: 0.015 ( 0 hom. )
Consequence
KANSL1
NM_015443.4 3_prime_UTR
NM_015443.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.844
Genes affected
KANSL1 (HGNC:24565): (KAT8 regulatory NSL complex subunit 1) This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 17-46030522-G-C is Benign according to our data. Variant chr17-46030522-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 323748.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00379 (571/150668) while in subpopulation NFE AF= 0.00588 (399/67820). AF 95% confidence interval is 0.00541. There are 0 homozygotes in gnomad4. There are 256 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 571 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.*954C>G | 3_prime_UTR_variant | 15/15 | ENST00000432791.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KANSL1 | ENST00000432791.7 | c.*954C>G | 3_prime_UTR_variant | 15/15 | 1 | NM_015443.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00379 AC: 571AN: 150548Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD4 exome AF: 0.0147 AC: 1AN: 68Hom.: 0 Cov.: 0 AF XY: 0.0227 AC XY: 1AN XY: 44
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GnomAD4 genome ? AF: 0.00379 AC: 571AN: 150668Hom.: 0 Cov.: 31 AF XY: 0.00348 AC XY: 256AN XY: 73484
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?
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256
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Syndromic intellectual disability Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | KANSL1: BS1 - |
Computational scores
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Name
Calibrated prediction
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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