1-197084463-GTTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018136.5(ASPM):c.10332-40_10332-38del 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 1,432,470 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (7 hom.)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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 -10 ACMG points.

• BP6: Variant 1-197084463-GTTC-G is Benign according to our data. Variant chr1-197084463-GTTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1220309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00521 (785/150634) while in subpopulation AFR AF= 0.0179 (737/41166). AF 95% confidence interval is 0.0168. There are 9 homozygotes in gnomad4. There are 355 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPM	NM_018136.5	c.10332-40_10332-38del		intron_variant		ENST00000367409.9
ASPM	NM_001206846.2	c.5577-40_5577-38del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPM	ENST00000367409.9	c.10332-40_10332-38del		intron_variant		1	NM_018136.5	P1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 786 AN: 150550 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00289

GnomAD3 exomes AF: 0.00128 AC: 291 AN: 227884 Hom.: 3 AF XY: 0.00102 AC XY: 127 AN XY: 124398

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.000391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000679

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000298

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000535 AC: 686 AN: 1281836 Hom.: 7 AF XY: 0.000481 AC XY: 311 AN XY: 646094

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.000666

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000609

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000188

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00521 AC: 785 AN: 150634 Hom.: 9 Cov.: 32 AF XY: 0.00484 AC XY: 355 AN XY: 73404

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.00265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00287

Alfa AF: 0.00326 Hom.: 4

Bravo AF: 0.00640

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs537718986; hg19: chr1-197053593;