rs12116571

Variant names:

• chr1-197119863-C-T
• rs12116571
• NM_018136.5:c.3871-1880G>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.3871-1880G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,106 control chromosomes in the GnomAD database, including 682 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 0.084 (682 hom., cov: 32)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5	c.3871-1880G>A		intron_variant	Intron 16 of 27	ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.3871-1880G>A		intron_variant	Intron 16 of 26		NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9	c.3871-1880G>A		intron_variant	Intron 16 of 27	1	NM_018136.5	ENSP00000356379.4

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12783 AN: 151988 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0781

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

GnomAD4 genome AF: 0.0840 AC: 12783 AN: 152106 Hom.: 682 Cov.: 32 AF XY: 0.0822 AC XY: 6115 AN XY: 74356

African (AFR) AF: 0.0367 AC: 1523 AN: 41494

American (AMR) AF: 0.0674 AC: 1030 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1412 AN: 10572

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7985 AN: 67976

Other (OTH) AF: 0.0773 AC: 163 AN: 2108

Alfa AF: 0.120 Hom.: 1059

Bravo AF: 0.0780

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.22
PhyloP100		-1.5
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: rs12116571; hg19: chr1-197088993;