Variant chr1-197086652-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018136.5(ASPM):c.10331+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 716,246 control chromosomes in the GnomAD database, including 278,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 50021 hom., cov: 33)

Exomes 𝑓: 0.90 ( 228499 hom. )

Consequence

ASPM
NM_018136.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.659

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 1-197086652-T-C is Benign according to our data. Variant chr1-197086652-T-C is described in ClinVar as [Benign]. Clinvar id is 678055.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPM	NM_018136.5 link	c.10331+151A>G		intron_variant		ENST00000367409.9	NP_060606.3	Q8IZT6-1B3KWI2
ASPM	NM_001206846.2 link	c.5576+151A>G		intron_variant			NP_001193775.1	Q8IZT6-2B3KWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 link	c.10331+151A>G		intron_variant		1	NM_018136.5	ENSP00000356379.4		Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119227

AN:

152084

Hom.:

49998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.902

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.813

GnomAD4 exome

AF:

0.896

AC:

505323

AN:

564046

Hom.:

228499

AF XY:

0.898

AC XY:

271784

AN XY:

302768

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.922

Gnomad4 ASJ exome

AF:

0.897

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.902

Gnomad4 OTH exome

AF:

0.879

GnomAD4 genome

AF:

0.784

AC:

119299

AN:

152200

Hom.:

50021

Cov.:

AF XY:

0.789

AC XY:

58687

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.872

Gnomad4 ASJ

AF:

0.902

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.899

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.815

Alfa

AF:

0.836

Hom.:

6870

Bravo

AF:

0.765

Asia WGS

AF:

0.918

AC:

3176

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.7

DANN

Benign

0.45

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