rs35451920
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198525.3(KIF7):c.2271C>T(p.Ala757=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,610,644 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0084 ( 18 hom., cov: 32)
Exomes 𝑓: 0.00086 ( 17 hom. )
Consequence
KIF7
NM_198525.3 synonymous
NM_198525.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 15-89642326-G-A is Benign according to our data. Variant chr15-89642326-G-A is described in ClinVar as [Benign]. Clinvar id is 129411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89642326-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-4.54 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00839 (1277/152118) while in subpopulation AFR AF= 0.0292 (1211/41520). AF 95% confidence interval is 0.0278. There are 18 homozygotes in gnomad4. There are 600 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 18 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF7 | NM_198525.3 | c.2271C>T | p.Ala757= | synonymous_variant | 11/19 | ENST00000394412.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF7 | ENST00000394412.8 | c.2271C>T | p.Ala757= | synonymous_variant | 11/19 | 5 | NM_198525.3 | P2 | |
KIF7 | ENST00000696512.1 | c.2394C>T | p.Ala798= | synonymous_variant | 11/19 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00837 AC: 1272AN: 152000Hom.: 18 Cov.: 32
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GnomAD3 exomes AF: 0.00210 AC: 511AN: 243070Hom.: 10 AF XY: 0.00154 AC XY: 203AN XY: 131998
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GnomAD4 exome AF: 0.000861 AC: 1256AN: 1458526Hom.: 17 Cov.: 32 AF XY: 0.000812 AC XY: 589AN XY: 725546
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GnomAD4 genome ? AF: 0.00839 AC: 1277AN: 152118Hom.: 18 Cov.: 32 AF XY: 0.00807 AC XY: 600AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 12, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Acrocallosal syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at