9-92461698-A-G

Variant names:

• chr9-92461698-A-G
• rs7033979
• NM_017680.6:c.713-1131T>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.713-1131T>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 152,042 control chromosomes in the GnomAD database, including 12,622 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 (12622 hom., cov: 32)
• Consequence: ASPN NM_017680.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 8 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 = 0.625 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.713-1131T>C		intron	N/A	NP_060150.4
	CENPP	NM_001012267.3	MANE Select	c.564+81839A>G		intron	N/A	NP_001012267.1
	ASPN	NM_001193335.3		c.712+3221T>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+81839A>G		intron	N/A	ENSP00000364737.3
	ASPN	ENST00000375544.7	TSL:1	c.713-1131T>C		intron	N/A	ENSP00000364694.3
	ASPN	ENST00000375543.2	TSL:2	c.712+3221T>C		intron	N/A	ENSP00000364693.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56019 AN: 151924 Hom.: 12596 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.369 AC: 56084 AN: 152042 Hom.: 12622 Cov.: 32 AF XY: 0.360 AC XY: 26738 AN XY: 74312

African (AFR) AF: 0.631 AC: 26161 AN: 41452

American (AMR) AF: 0.266 AC: 4061 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1196 AN: 3472

East Asian (EAS) AF: 0.106 AC: 547 AN: 5164

South Asian (SAS) AF: 0.150 AC: 725 AN: 4828

European-Finnish (FIN) AF: 0.249 AC: 2632 AN: 10570

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19382 AN: 67966

Other (OTH) AF: 0.366 AC: 771 AN: 2108

Alfa AF: 0.271 Hom.: 993

Bravo AF: 0.385

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		-0.47
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: rs7033979; hg19: chr9-95223980;