1-197086652-T-C

Variant names:

• chr1-197086652-T-C
• rs10733087
• NM_018136.5:c.10331+151A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018136.5(ASPM):​c.10331+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 716,246 control chromosomes in the GnomAD database, including 278,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (50021 hom., cov: 33)
  • Exomes 𝑓: 0.90 (228499 hom.)
• Consequence: ASPM NM_018136.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.659
• 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):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• microcephaly 5, primary, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 1-197086652-T-C is Benign according to our data. Variant chr1-197086652-T-C is described in ClinVar as Benign. ClinVar VariationId is 678055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPM	NM_018136.5	MANE Select	c.10331+151A>G		intron	N/A	NP_060606.3
	ASPM	NM_001206846.2		c.5576+151A>G		intron	N/A	NP_001193775.1	Q8IZT6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPM	ENST00000367409.9	TSL:1 MANE Select	c.10331+151A>G		intron	N/A	ENSP00000356379.4	Q8IZT6-1
	ASPM	ENST00000294732.11	TSL:1	c.5576+151A>G		intron	N/A	ENSP00000294732.7	Q8IZT6-2
	ASPM	ENST00000367408.6	TSL:1	n.3618+151A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119227 AN: 152084 Hom.: 49998 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.896 AC: 505323 AN: 564046 Hom.: 228499 AF XY: 0.898 AC XY: 271784 AN XY: 302768

African (AFR) AF: 0.442 AC: 7075 AN: 16014

American (AMR) AF: 0.922 AC: 26968 AN: 29264

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 14698 AN: 16386

East Asian (EAS) AF: 1.00 AC: 34312 AN: 34316

South Asian (SAS) AF: 0.895 AC: 49063 AN: 54792

European-Finnish (FIN) AF: 0.931 AC: 33273 AN: 35722

Middle Eastern (MID) AF: 0.860 AC: 1902 AN: 2212

European-Non Finnish (NFE) AF: 0.902 AC: 311621 AN: 345308

Other (OTH) AF: 0.879 AC: 26411 AN: 30032

GnomAD4 genome AF: 0.784 AC: 119299 AN: 152200 Hom.: 50021 Cov.: 33 AF XY: 0.789 AC XY: 58687 AN XY: 74408

African (AFR) AF: 0.451 AC: 18712 AN: 41494

American (AMR) AF: 0.872 AC: 13327 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3133 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5186

South Asian (SAS) AF: 0.899 AC: 4331 AN: 4820

European-Finnish (FIN) AF: 0.929 AC: 9841 AN: 10596

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61913 AN: 68018

Other (OTH) AF: 0.815 AC: 1725 AN: 2116

Alfa AF: 0.821 Hom.: 6954

Bravo AF: 0.765

Asia WGS AF: 0.918 AC: 3176 AN: 3460

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.66
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: rs10733087; hg19: chr1-197055782;