15-48744295-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001194998.2(CEP152):āc.3780G>Cā(p.Gly1260Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,852 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: š 0.00018 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
CEP152
NM_001194998.2 synonymous
NM_001194998.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0240
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 15-48744295-C-G is Benign according to our data. Variant chr15-48744295-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 316412.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=1}.
BP7
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CEP152 | NM_001194998.2 | c.3780G>C | p.Gly1260Gly | synonymous_variant | 24/27 | ENST00000380950.7 | NP_001181927.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CEP152 | ENST00000380950.7 | c.3780G>C | p.Gly1260Gly | synonymous_variant | 24/27 | 1 | NM_001194998.2 | ENSP00000370337.2 | ||
| CEP152 | ENST00000399334.7 | c.3612G>C | p.Gly1204Gly | synonymous_variant | 23/26 | 1 | ENSP00000382271.3 | |||
| CEP152 | ENST00000325747.9 | c.3501G>C | p.Gly1167Gly | synonymous_variant | 23/25 | 1 | ENSP00000321000.5 |
Frequencies
GnomAD3 genomes 0.000178 AC: 27AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000285 AC: 71AN: 249522Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 135372
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GnomAD4 exome AF: 0.000154 AC: 225AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 727174
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GnomAD4 genome 0.000178 AC: 27AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74296
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
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. - |
Seckel syndrome 5 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. - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 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. - |
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | - - |
Computational scores
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RBP_binding_hub_radar
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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