1-197141692-A-G

Variant names:

• chr1-197141692-A-G
• rs1888991
• NM_018136.5:c.1921+639T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018136.5(ASPM):​c.1921+639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,106 control chromosomes in the GnomAD database, including 49,471 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 0.78 (49471 hom., cov: 31)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5	c.1921+639T>C		intron_variant	Intron 3 of 27	ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.1921+639T>C		intron_variant	Intron 3 of 26		NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9	c.1921+639T>C		intron_variant	Intron 3 of 27	1	NM_018136.5	ENSP00000356379.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118032 AN: 151988 Hom.: 49450 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.776 AC: 118102 AN: 152106 Hom.: 49471 Cov.: 31 AF XY: 0.782 AC XY: 58147 AN XY: 74368

African (AFR) AF: 0.426 AC: 17652 AN: 41482

American (AMR) AF: 0.870 AC: 13291 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3128 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5170

South Asian (SAS) AF: 0.898 AC: 4332 AN: 4822

European-Finnish (FIN) AF: 0.929 AC: 9846 AN: 10604

Middle Eastern (MID) AF: 0.901 AC: 263 AN: 292

European-Non Finnish (NFE) AF: 0.910 AC: 61849 AN: 67964

Other (OTH) AF: 0.808 AC: 1704 AN: 2110

Alfa AF: 0.802 Hom.: 7862

Bravo AF: 0.756

Asia WGS AF: 0.918 AC: 3193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		0.15
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: rs1888991; hg19: chr1-197110822;