rs1571964

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018136.5(ASPM):c.441+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,592,502 control chromosomes in the GnomAD database, including 628,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 48502 hom., cov: 32)

Exomes 𝑓: 0.89 ( 579878 hom. )

Consequence

ASPM
NM_018136.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.198

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

microcephaly 5, primary, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive primary microcephaly
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

ASPM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-197143943-G-A is Benign according to our data. Variant chr1-197143943-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5 link	c.441+14C>T		intron_variant	Intron 2 of 27	ENST00000367409.9	NP_060606.3	Q8IZT6-1B3KWI2
ASPM	NM_001206846.2 link	c.441+14C>T		intron_variant	Intron 2 of 26		NP_001193775.1	Q8IZT6-2B3KWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 link	c.441+14C>T		intron_variant	Intron 2 of 27	1	NM_018136.5	ENSP00000356379.4		Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115902

AN:

151942

Hom.:

48485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.798

GnomAD2 exomes

AF:

0.880

AC:

218135

AN:

247926

AF XY:

0.888

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.931

Gnomad ASJ exome

AF:

0.893

Gnomad EAS exome

AF:

0.982

Gnomad FIN exome

AF:

0.930

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.895

GnomAD4 exome

AF:

0.893

AC:

1286303

AN:

1440440

Hom.:

579878

Cov.:

AF XY:

0.895

AC XY:

642143

AN XY:

717692

show subpopulations

African (AFR)

AF:

0.358

AC:

11871

AN:

33186

American (AMR)

AF:

0.925

AC:

41203

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

23303

AN:

25916

East Asian (EAS)

AF:

0.982

AC:

38736

AN:

39448

South Asian (SAS)

AF:

0.898

AC:

76713

AN:

85432

European-Finnish (FIN)

AF:

0.932

AC:

49504

AN:

53112

Middle Eastern (MID)

AF:

0.863

AC:

4899

AN:

5674

European-Non Finnish (NFE)

AF:

0.903

AC:

987805

AN:

1093494

Other (OTH)

AF:

0.877

AC:

52269

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

5671

11342

17014

22685

28356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20882

41764

62646

83528

104410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.763

AC:

115960

AN:

152062

Hom.:

48502

Cov.:

AF XY:

0.768

AC XY:

57133

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.380

AC:

15706

AN:

41380

American (AMR)

AF:

0.864

AC:

13205

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

3130

AN:

3472

East Asian (EAS)

AF:

0.979

AC:

5070

AN:

5178

South Asian (SAS)

AF:

0.898

AC:

4337

AN:

4828

European-Finnish (FIN)

AF:

0.929

AC:

9846

AN:

10604

Middle Eastern (MID)

AF:

0.891

AC:

262

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61841

AN:

67986

Other (OTH)

AF:

0.800

AC:

1692

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

966

1931

2897

3862

4828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.818

Hom.:

11314

Bravo

AF:

0.741

Asia WGS

AF:

0.909

AC:

3147

AN:

3464

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 5, primary, autosomal recessive

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 31, 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

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

not specified

Benign:4

Feb 07, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

- -

Mar 03, 2015

GeneDx

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

-0.79

CADD

Benign

4.5

(source)

DANN

Benign

0.37

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over