rs149478199
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001194998.2(CEP152):āc.4072C>Gā(p.Gln1358Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000369 in 1,614,074 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0019 ( 1 hom., cov: 32)
Exomes š: 0.00021 ( 3 hom. )
Consequence
CEP152
NM_001194998.2 missense
NM_001194998.2 missense
Scores
1
1
16
Clinical Significance
Conservation
PhyloP100: 3.91
Genes affected
CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]
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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 (MetaRNN=0.0039657354).
BP6
?
Variant 15-48741622-G-C is Benign according to our data. Variant chr15-48741622-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158262.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=4, Uncertain_significance=1}. Variant chr15-48741622-G-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00192 (292/152248) while in subpopulation AFR AF= 0.00662 (275/41548). AF 95% confidence interval is 0.00598. There are 1 homozygotes in gnomad4. There are 121 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.4072C>G | p.Gln1358Glu | missense_variant | 26/27 | ENST00000380950.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.4072C>G | p.Gln1358Glu | missense_variant | 26/27 | 1 | NM_001194998.2 | A2 | |
CEP152 | ENST00000399334.7 | c.3904C>G | p.Gln1302Glu | missense_variant | 25/26 | 1 | P2 | ||
CEP152 | ENST00000325747.9 | c.3793C>G | p.Gln1265Glu | missense_variant | 25/25 | 1 | A2 | ||
CEP152 | ENST00000561245.1 | c.142+9C>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00192 AC: 292AN: 152130Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000405 AC: 101AN: 249398Hom.: 1 AF XY: 0.000310 AC XY: 42AN XY: 135302
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GnomAD4 exome AF: 0.000208 AC: 304AN: 1461826Hom.: 3 Cov.: 32 AF XY: 0.000182 AC XY: 132AN XY: 727208
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GnomAD4 genome ? AF: 0.00192 AC: 292AN: 152248Hom.: 1 Cov.: 32 AF XY: 0.00163 AC XY: 121AN XY: 74444
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | CEP152: BP4 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 20, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 22, 2015 | - - |
Microcephaly 9, primary, autosomal recessive Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
CEP152-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Seckel syndrome 5 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.073
.;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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