rs4915337

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018136.5(ASPM):c.3579T>A(p.Ser1193Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,613,582 control chromosomes in the GnomAD database, including 641,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 49988 hom., cov: 32)

Exomes 𝑓: 0.90 ( 591199 hom. )

Consequence

ASPM
NM_018136.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -0.295

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]

ASPM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-197122407-A-T is Benign according to our data. Variant chr1-197122407-A-T is described in ClinVar as [Benign]. Clinvar id is 21578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197122407-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.295 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5 link	c.3579T>A	p.Ser1193Ser	synonymous_variant	Exon 14 of 28	ENST00000367409.9	NP_060606.3	Q8IZT6-1B3KWI2
ASPM	NM_001206846.2 link	c.3579T>A	p.Ser1193Ser	synonymous_variant	Exon 14 of 27		NP_001193775.1	Q8IZT6-2B3KWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 link	c.3579T>A	p.Ser1193Ser	synonymous_variant	Exon 14 of 28	1	NM_018136.5	ENSP00000356379.4		Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119166

AN:

152002

Hom.:

49965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.814

GnomAD3 exomes

AF:

0.887

AC:

222653

AN:

250926

Hom.:

100699

AF XY:

0.894

AC XY:

121249

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.443

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.893

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.899

Gnomad FIN exome

AF:

0.930

Gnomad NFE exome

AF:

0.906

Gnomad OTH exome

AF:

0.899

GnomAD4 exome

AF:

0.896

AC:

1309791

AN:

1461462

Hom.:

591199

Cov.:

AF XY:

0.898

AC XY:

652601

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.434

Gnomad4 AMR exome

AF:

0.929

Gnomad4 ASJ exome

AF:

0.899

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.899

Gnomad4 FIN exome

AF:

0.932

Gnomad4 NFE exome

AF:

0.904

Gnomad4 OTH exome

AF:

0.883

GnomAD4 genome

AF:

0.784

AC:

119239

AN:

152120

Hom.:

49988

Cov.:

AF XY:

0.789

AC XY:

58651

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.872

Gnomad4 ASJ

AF:

0.901

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.898

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.902

Hom.:

47170

Bravo

AF:

0.765

Asia WGS

AF:

0.920

AC:

3198

AN:

3478

EpiCase

AF:

0.906

EpiControl

AF:

0.909

ClinVar

Significance: Benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 5, primary, autosomal recessive

Benign:4Other:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over