rs56912014

Positions:

chr1-197117942-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000367409.9(ASPM):c.3912C>A(p.Ile1304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,613,374 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 41 hom. )

Consequence

ASPM
ENST00000367409.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.00900

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=-0.79).

BP6

Variant 1-197117942-G-T is Benign according to our data. Variant chr1-197117942-G-T is described in ClinVar as [Benign]. Clinvar id is 157814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197117942-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.009 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2046/152042) while in subpopulation AFR AF= 0.046 (1909/41470). AF 95% confidence interval is 0.0443. There are 47 homozygotes in gnomad4. There are 972 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPM	NM_018136.5 linkuse as main transcript	c.3912C>A	p.Ile1304=	synonymous_variant	17/28	ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2 linkuse as main transcript	c.3912C>A	p.Ile1304=	synonymous_variant	17/27		NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 linkuse as main transcript	c.3912C>A	p.Ile1304=	synonymous_variant	17/28	1	NM_018136.5	ENSP00000356379	P1	Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2042

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0461

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00637

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00358

AC:

897

AN:

250414

Hom.:

AF XY:

0.00271

AC XY:

367

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00147

AC:

2151

AN:

1461332

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

943

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.0135

AC:

2046

AN:

152042

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

972

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0460

Gnomad4 AMR

AF:

0.00636

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00531

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00145

AC:

AN:

3472

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 08, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Microcephaly 5, primary, autosomal recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.61

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