rs13301537

Variant names:

• chr9-92466765-A-G
• rs13301537
• NM_017680.6:c.388-194T>C

Variant summary

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

The NM_017680.6(ASPN):​c.388-194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,050 control chromosomes in the GnomAD database, including 12,653 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 0.37 (12653 hom., cov: 32)
• Consequence: ASPN NM_017680.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 14 publications found

Genes affected

ASPN (HGNC:14872): (asporin) This gene encodes a cartilage extracellular protein that is member of the small leucine-rich proteoglycan family. The encoded protein may regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression in cartilage. This protein also binds collagen and calcium and may induce collagen mineralization. Polymorphisms in the aspartic acid repeat region of this gene are associated with a susceptibility to osteoarthritis, and also with intervertebral disc disease. Alternative splicing of this gene results in multiple transcript variants.[provided by RefSeq, Jul 2014]

CENPP (HGNC:32933): (centromere protein P) CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM 117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006 [PubMed 16622420]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017680.6. 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
	ASPN	NM_017680.6	MANE Select	c.388-194T>C		intron	N/A	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+86906A>G		intron	N/A	NP_001012267.1
	ASPN	NM_001193335.3		c.388-194T>C		intron	N/A	NP_001180264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPP	ENST00000375587.8	TSL:1 MANE Select	c.564+86906A>G		intron	N/A	ENSP00000364737.3
	ASPN	ENST00000375544.7	TSL:1	c.388-194T>C		intron	N/A	ENSP00000364694.3
	ASPN	ENST00000375543.2	TSL:2	c.388-194T>C		intron	N/A	ENSP00000364693.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56054 AN: 151932 Hom.: 12626 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.369 AC: 56121 AN: 152050 Hom.: 12653 Cov.: 32 AF XY: 0.360 AC XY: 26762 AN XY: 74338

African (AFR) AF: 0.632 AC: 26191 AN: 41432

American (AMR) AF: 0.267 AC: 4079 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3472

East Asian (EAS) AF: 0.108 AC: 559 AN: 5172

South Asian (SAS) AF: 0.148 AC: 715 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2638 AN: 10574

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19359 AN: 67970

Other (OTH) AF: 0.367 AC: 774 AN: 2110

Alfa AF: 0.319 Hom.: 10953

Bravo AF: 0.386

Asia WGS AF: 0.148 AC: 516 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.055
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: rs13301537; hg19: chr9-95229047;