rs141108591
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000367409.9(ASPM):c.-9G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,605,288 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00077 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00059 ( 11 hom. )
Consequence
ASPM
ENST00000367409.9 5_prime_UTR
ENST00000367409.9 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.258
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=-0.78).
BP6
Variant 1-197146446-C-A is Benign according to our data. Variant chr1-197146446-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 157768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000769 (117/152132) while in subpopulation EAS AF= 0.0212 (109/5130). AF 95% confidence interval is 0.018. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.-9G>T | 5_prime_UTR_variant | 1/28 | ENST00000367409.9 | NP_060606.3 | ||
ASPM | NM_001206846.2 | c.-9G>T | 5_prime_UTR_variant | 1/27 | NP_001193775.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.-9G>T | 5_prime_UTR_variant | 1/28 | 1 | NM_018136.5 | ENSP00000356379 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000770 AC: 117AN: 152010Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00195 AC: 450AN: 231340Hom.: 5 AF XY: 0.00185 AC XY: 237AN XY: 127958
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GnomAD4 exome AF: 0.000594 AC: 863AN: 1453156Hom.: 11 Cov.: 31 AF XY: 0.000603 AC XY: 436AN XY: 722930
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GnomAD4 genome AF: 0.000769 AC: 117AN: 152132Hom.: 0 Cov.: 31 AF XY: 0.000928 AC XY: 69AN XY: 74382
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
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 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 23, 2015 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2018 | - - |
Computational scores
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Name
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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