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GeneBe

rs4915344

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018136.5(ASPM):c.2174-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,607,116 control chromosomes in the GnomAD database, including 39,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3872 hom., cov: 32)
Exomes 𝑓: 0.19 ( 35883 hom. )

Consequence

ASPM
NM_018136.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.883
Variant links:
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=-0.72).
BP6
Variant 1-197133615-A-G is Benign according to our data. Variant chr1-197133615-A-G is described in ClinVar as [Benign]. Clinvar id is 95887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197133615-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.2174-20T>C intron_variant ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.2174-20T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.2174-20T>C intron_variant 1 NM_018136.5 P1Q8IZT6-1

Frequencies

GnomAD3 genomes
AF:
0.176
AC:
26819
AN:
152042
Hom.:
3862
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0444
Gnomad AMI
AF:
0.0647
Gnomad AMR
AF:
0.333
Gnomad ASJ
AF:
0.191
Gnomad EAS
AF:
0.695
Gnomad SAS
AF:
0.310
Gnomad FIN
AF:
0.249
Gnomad MID
AF:
0.114
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.194
GnomAD3 exomes
AF:
0.257
AC:
64373
AN:
250084
Hom.:
12228
AF XY:
0.249
AC XY:
33714
AN XY:
135262
show subpopulations
Gnomad AFR exome
AF:
0.0421
Gnomad AMR exome
AF:
0.464
Gnomad ASJ exome
AF:
0.183
Gnomad EAS exome
AF:
0.705
Gnomad SAS exome
AF:
0.281
Gnomad FIN exome
AF:
0.249
Gnomad NFE exome
AF:
0.157
Gnomad OTH exome
AF:
0.218
GnomAD4 exome
AF:
0.192
AC:
279570
AN:
1454956
Hom.:
35883
Cov.:
31
AF XY:
0.194
AC XY:
140251
AN XY:
724216
show subpopulations
Gnomad4 AFR exome
AF:
0.0364
Gnomad4 AMR exome
AF:
0.454
Gnomad4 ASJ exome
AF:
0.179
Gnomad4 EAS exome
AF:
0.684
Gnomad4 SAS exome
AF:
0.281
Gnomad4 FIN exome
AF:
0.241
Gnomad4 NFE exome
AF:
0.159
Gnomad4 OTH exome
AF:
0.208
GnomAD4 genome
AF:
0.176
AC:
26836
AN:
152160
Hom.:
3872
Cov.:
32
AF XY:
0.189
AC XY:
14046
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0443
Gnomad4 AMR
AF:
0.334
Gnomad4 ASJ
AF:
0.191
Gnomad4 EAS
AF:
0.695
Gnomad4 SAS
AF:
0.310
Gnomad4 FIN
AF:
0.249
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.197
Alfa
AF:
0.159
Hom.:
509
Bravo
AF:
0.180
Asia WGS
AF:
0.486
AC:
1690
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 17, 2013This 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. -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 19, 2014- -
Microcephaly 5, primary, autosomal recessive Benign:3
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical CenterMay 31, 2017- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
9.1
Dann
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4915344; hg19: chr1-197102745; COSMIC: COSV54132578; API