1-197107064-C-T

Position:

• chr1-197107064-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018136.5(ASPM):​c.4066-1879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,814 control chromosomes in the GnomAD database, including 16,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (16584 hom., cov: 31)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPM	NM_018136.5	c.4066-1879G>A		intron_variant		ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.4065+10725G>A		intron_variant			NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9	c.4066-1879G>A		intron_variant		1	NM_018136.5	ENSP00000356379.4

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67078 AN: 151696 Hom.: 16572 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.442 AC: 67110 AN: 151814 Hom.: 16584 Cov.: 31 AF XY: 0.452 AC XY: 33527 AN XY: 74150

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.462

Alfa AF: 0.467 Hom.: 7807

Bravo AF: 0.439

Asia WGS AF: 0.702 AC: 2440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.36

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: rs10801589; hg19: chr1-197076194;