rs141600901
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBS1BS2
The NM_001194998.2(CEP152):βc.4378_4379delβ(p.Val1460PhefsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,614,180 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0041 ( 3 hom., cov: 32)
Exomes π: 0.00039 ( 7 hom. )
Consequence
CEP152
NM_001194998.2 frameshift
NM_001194998.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.136
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 -12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.147 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BP6
?
Variant 15-48739002-AAC-A is Benign according to our data. Variant chr15-48739002-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 31033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48739002-AAC-A is described in Lovd as [Pathogenic].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (628/152330) while in subpopulation AFR AF= 0.0146 (608/41576). AF 95% confidence interval is 0.0137. There are 3 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP152 | NM_001194998.2 | c.4378_4379del | p.Val1460PhefsTer3 | frameshift_variant | 27/27 | ENST00000380950.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.4378_4379del | p.Val1460PhefsTer3 | frameshift_variant | 27/27 | 1 | NM_001194998.2 | A2 | |
CEP152 | ENST00000399334.7 | c.4210_4211del | p.Val1404PhefsTer3 | frameshift_variant | 26/26 | 1 | P2 | ||
CEP152 | ENST00000561245.1 | c.142+2627_142+2628del | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00413 AC: 628AN: 152212Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00108 AC: 270AN: 249228Hom.: 4 AF XY: 0.000814 AC XY: 110AN XY: 135196
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GnomAD4 exome AF: 0.000391 AC: 572AN: 1461850Hom.: 7 AF XY: 0.000351 AC XY: 255AN XY: 727218
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GnomAD4 genome ? AF: 0.00412 AC: 628AN: 152330Hom.: 3 Cov.: 32 AF XY: 0.00381 AC XY: 284AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:1Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | CEP152: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2020 | This variant is associated with the following publications: (PMID: 21131973) - |
Seckel syndrome 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2011 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 18, 2015 | - - |
Computational scores
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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