1-197117000-T-C

Position:

• chr1-197117000-T-C

Variant summary

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

The ENST00000367409.9(ASPM):​c.4065+789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,092 control chromosomes in the GnomAD database, including 3,873 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 0.18 (3873 hom., cov: 32)
• Consequence: ASPM ENST00000367409.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPM	NM_018136.5	c.4065+789A>G		intron_variant		ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.4065+789A>G		intron_variant			NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9	c.4065+789A>G		intron_variant		1	NM_018136.5	ENSP00000356379	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26855 AN: 151974 Hom.: 3864 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.177 AC: 26871 AN: 152092 Hom.: 3873 Cov.: 32 AF XY: 0.189 AC XY: 14048 AN XY: 74314

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.195

Alfa AF: 0.183 Hom.: 575

Bravo AF: 0.181

Asia WGS AF: 0.484 AC: 1678 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.63

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: rs10922168; hg19: chr1-197086130;