rs41310925

Variant names:

• chr1-197103290-T-C
• rs41310925
• NM_018136.5:c.5961A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-197103290-T-C
• chr1-197103290-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018136.5(ASPM):​c.5961A>G​(p.Gln1987Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,612,890 control chromosomes in the GnomAD database, including 129,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8815 hom., cov: 32)
  • Exomes 𝑓: 0.40 (120943 hom.)
• Consequence: ASPM NM_018136.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11 O:1
• Conservation: PhyloP100: -2.90
• Publications: 18 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: Labcorp Genetics (formerly Invitae), G2P

ENSG00000300054 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-197103290-T-C is Benign according to our data. Variant chr1-197103290-T-C is described in ClinVar as Benign. ClinVar VariationId is 21593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 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.5961A>G	p.Gln1987Gln	synonymous	Exon 18 of 28	NP_060606.3
	ASPM	NM_001206846.2		c.4066-7126A>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.5961A>G	p.Gln1987Gln	synonymous	Exon 18 of 28	ENSP00000356379.4	Q8IZT6-1
	ASPM	ENST00000294732.11	TSL:1	c.4066-7126A>G		intron	N/A	ENSP00000294732.7	Q8IZT6-2
	ASPM	ENST00000367408.6	TSL:1	n.2108-7126A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46036 AN: 151720 Hom.: 8819 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.331

GnomAD2 exomes AF: 0.335 AC: 83931 AN: 250246 AF XY: 0.346

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.397 AC: 580747 AN: 1461052 Hom.: 120943 Cov.: 51 AF XY: 0.397 AC XY: 288248 AN XY: 726844

African (AFR) AF: 0.0760 AC: 2541 AN: 33438

American (AMR) AF: 0.217 AC: 9670 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 10258 AN: 26104

East Asian (EAS) AF: 0.154 AC: 6110 AN: 39684

South Asian (SAS) AF: 0.308 AC: 26557 AN: 86232

European-Finnish (FIN) AF: 0.370 AC: 19751 AN: 53328

Middle Eastern (MID) AF: 0.371 AC: 2139 AN: 5760

European-Non Finnish (NFE) AF: 0.433 AC: 481292 AN: 1111536

Other (OTH) AF: 0.372 AC: 22429 AN: 60340

GnomAD4 genome AF: 0.303 AC: 46035 AN: 151838 Hom.: 8815 Cov.: 32 AF XY: 0.299 AC XY: 22177 AN XY: 74224

African (AFR) AF: 0.0886 AC: 3678 AN: 41496

American (AMR) AF: 0.267 AC: 4061 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3470

East Asian (EAS) AF: 0.156 AC: 803 AN: 5134

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3945 AN: 10598

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29560 AN: 67806

Other (OTH) AF: 0.329 AC: 693 AN: 2104

Alfa AF: 0.387 Hom.: 8104

Bravo AF: 0.284

Asia WGS AF: 0.202 AC: 706 AN: 3476

EpiCase AF: 0.422

EpiControl AF: 0.426

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Microcephaly 5, primary, autosomal recessive (5)
-	-	4	not specified (4)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.30
PhyloP100		-2.9
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: rs41310925; hg19: chr1-197072420; COSMIC: COSV54124262;