rs1537318
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_018136.5(ASPM):c.*60C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,258,850 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 96 hom., cov: 31)
Exomes 𝑓: 0.0025 ( 69 hom. )
Consequence
ASPM
NM_018136.5 3_prime_UTR
NM_018136.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.47
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 1-197084264-G-A is Benign according to our data. Variant chr1-197084264-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.*60C>T | 3_prime_UTR_variant | 28/28 | ENST00000367409.9 | NP_060606.3 | ||
ASPM | NM_001206846.2 | c.*60C>T | 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.*60C>T | 3_prime_UTR_variant | 28/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 | ||
ASPM | ENST00000294732.11 | c.*60C>T | 3_prime_UTR_variant | 27/27 | 1 | ENSP00000294732 | ||||
ASPM | ENST00000367408.6 | n.3781C>T | non_coding_transcript_exon_variant | 18/18 | 1 | |||||
ASPM | ENST00000680265.1 | c.*60C>T | 3_prime_UTR_variant | 29/29 | ENSP00000505384 |
Frequencies
GnomAD3 genomes AF: 0.0209 AC: 3166AN: 151806Hom.: 96 Cov.: 31
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GnomAD4 exome AF: 0.00249 AC: 2760AN: 1106926Hom.: 69 Cov.: 15 AF XY: 0.00215 AC XY: 1218AN XY: 566476
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GnomAD4 genome AF: 0.0209 AC: 3173AN: 151924Hom.: 96 Cov.: 31 AF XY: 0.0198 AC XY: 1472AN XY: 74232
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Benign:2
Likely benign, 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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