chr1-197107064-C-T

Variant names:

• chr1-197107064-C-T
• rs10801589
• NM_018136.5:c.4066-1879G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 5, primary, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPM	NM_018136.5	MANE Select	c.4066-1879G>A		intron	N/A	NP_060606.3
	ASPM	NM_001206846.2		c.4065+10725G>A		intron	N/A	NP_001193775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPM	ENST00000367409.9	TSL:1 MANE Select	c.4066-1879G>A		intron	N/A	ENSP00000356379.4
	ASPM	ENST00000294732.11	TSL:1	c.4065+10725G>A		intron	N/A	ENSP00000294732.7
	ASPM	ENST00000367408.6	TSL:1	n.2107+10725G>A		intron	N/A

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

African (AFR) AF: 0.235 AC: 9725 AN: 41444

American (AMR) AF: 0.591 AC: 8980 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1695 AN: 3470

East Asian (EAS) AF: 0.822 AC: 4202 AN: 5110

South Asian (SAS) AF: 0.605 AC: 2916 AN: 4816

European-Finnish (FIN) AF: 0.557 AC: 5865 AN: 10532

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32128 AN: 67926

Other (OTH) AF: 0.462 AC: 975 AN: 2112

Alfa AF: 0.465 Hom.: 8690

Bravo AF: 0.439

Asia WGS AF: 0.702 AC: 2440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.36
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10801589; hg19: chr1-197076194;