rs200804798

chr1-197095951-TCACA-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_018136.5(ASPM):c.8987+43_8987+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,483,714 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (6 hom.)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.904

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 -9 ACMG points.

• BP6: Variant 1-197095951-TCACA-T is Benign according to our data. Variant chr1-197095951-TCACA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210362.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00405 (615/151896) while in subpopulation AFR AF= 0.0128 (532/41496). AF 95% confidence interval is 0.0119. There are 7 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPM	NM_018136.5	c.8987+43_8987+46del		intron_variant		ENST00000367409.9
ASPM	NM_001206846.2	c.4232+43_4232+46del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPM	ENST00000367409.9	c.8987+43_8987+46del		intron_variant		1	NM_018136.5	P1

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 603 AN: 151778 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00147 AC: 342 AN: 232480 Hom.: 3 AF XY: 0.00128 AC XY: 161 AN XY: 125670

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000293

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000380

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.000690 AC: 919 AN: 1331818 Hom.: 6 AF XY: 0.000654 AC XY: 434 AN XY: 663510

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.000523

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000382

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000813

Gnomad4 OTH exome AF: 0.00203

GnomAD4 genome AF: 0.00405 AC: 615 AN: 151896 Hom.: 7 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74254

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000737

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00387 Hom.: 3

Bravo AF: 0.00440

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs200804798; hg19: chr1-197065081;