1-197084166-A-G
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_018136.5(ASPM):c.*158T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 623,186 control chromosomes in the GnomAD database, including 72 homozygotes. 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: 𝑓 0.0084 ( 14 hom., cov: 32)
Exomes 𝑓: 0.011 ( 58 hom. )
Consequence
ASPM
NM_018136.5 3_prime_UTR
NM_018136.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.590
Genes affected
ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]
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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 (BayesDel_noAF=-0.81).
BP6
Variant 1-197084166-A-G is Benign according to our data. Variant chr1-197084166-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210340.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00839 (1278/152306) while in subpopulation NFE AF= 0.0133 (906/68002). AF 95% confidence interval is 0.0126. There are 14 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.*158T>C | 3_prime_UTR_variant | 28/28 | ENST00000367409.9 | NP_060606.3 | ||
ASPM | NM_001206846.2 | c.*158T>C | 3_prime_UTR_variant | 27/27 | NP_001193775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.*158T>C | 3_prime_UTR_variant | 28/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 | ||
ASPM | ENST00000294732.11 | c.*158T>C | 3_prime_UTR_variant | 27/27 | 1 | ENSP00000294732 | ||||
ASPM | ENST00000367408.6 | n.3879T>C | non_coding_transcript_exon_variant | 18/18 | 1 | |||||
ASPM | ENST00000680265.1 | c.*158T>C | 3_prime_UTR_variant | 29/29 | ENSP00000505384 |
Frequencies
GnomAD3 genomes AF: 0.00842 AC: 1282AN: 152188Hom.: 14 Cov.: 32
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GnomAD4 exome AF: 0.0113 AC: 5343AN: 470880Hom.: 58 Cov.: 5 AF XY: 0.0114 AC XY: 2869AN XY: 251538
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GnomAD4 genome AF: 0.00839 AC: 1278AN: 152306Hom.: 14 Cov.: 32 AF XY: 0.00787 AC XY: 586AN XY: 74462
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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
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | ASPM: BS1, BS2 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Microcephaly 5, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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