chr15-89629369-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_198525.3(KIF7):c.3517+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,583,102 control chromosomes in the GnomAD database, including 82,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.26 ( 5835 hom., cov: 28)
Exomes 𝑓: 0.32 ( 76748 hom. )
Consequence
KIF7
NM_198525.3 splice_donor_region, intron
NM_198525.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001589
2
Clinical Significance
Conservation
PhyloP100: 0.304
Genes affected
KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]
TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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=-0.82).
BP6
Variant 15-89629369-G-A is Benign according to our data. Variant chr15-89629369-G-A is described in ClinVar as [Benign]. Clinvar id is 129416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89629369-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.3517+6C>T | splice_donor_region_variant, intron_variant | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.3517+6C>T | splice_donor_region_variant, intron_variant | 5 | NM_198525.3 | P2 | |||
TICRR | ENST00000561095.1 | c.*97-61G>A | intron_variant, NMD_transcript_variant | 1 | |||||
KIF7 | ENST00000696512.1 | c.3640+6C>T | splice_donor_region_variant, intron_variant | A2 | |||||
KIF7 | ENST00000677187.1 | n.1191+6C>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.261 AC: 39296AN: 150468Hom.: 5835 Cov.: 28
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GnomAD3 exomes AF: 0.308 AC: 71590AN: 232426Hom.: 11588 AF XY: 0.316 AC XY: 39990AN XY: 126614
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GnomAD4 exome AF: 0.324 AC: 463632AN: 1432522Hom.: 76748 Cov.: 35 AF XY: 0.326 AC XY: 232044AN XY: 711154
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GnomAD4 genome AF: 0.261 AC: 39296AN: 150580Hom.: 5835 Cov.: 28 AF XY: 0.261 AC XY: 19194AN XY: 73460
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ClinVar
Significance: Benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:8
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Acrocallosal syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Hydrolethalus syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Multiple epiphyseal dysplasia, Al-Gazali type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at