rs955927

chr1-197091653-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018136.5(ASPM):c.9444+254T>A variant causes a intron change. The variant allele was found at a frequency of 0.299 in 151,840 control chromosomes in the GnomAD database, including 8,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8482 hom., cov: 31)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.75

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-197091653-A-T is Benign according to our data. Variant chr1-197091653-A-T is described in ClinVar as [Benign]. Clinvar id is 668875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPM	NM_018136.5	c.9444+254T>A		intron_variant		ENST00000367409.9
ASPM	NM_001206846.2	c.4689+254T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPM	ENST00000367409.9	c.9444+254T>A		intron_variant		1	NM_018136.5	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45391 AN: 151722 Hom.: 8485 Cov.: 31

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45392 AN: 151840 Hom.: 8482 Cov.: 31 AF XY: 0.295 AC XY: 21870 AN XY: 74182

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.325

Alfa AF: 0.367 Hom.: 1451

Bravo AF: 0.280

Asia WGS AF: 0.198 AC: 691 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.74
Cadd	Benign	14
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs955927; hg19: chr1-197060783;