rs13301537

Positions:

• chr9-92466765-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012267.3(CENPP):​c.564+86906A>G 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: CENPP NM_001012267.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPP	NM_001012267.3	c.564+86906A>G		intron_variant		ENST00000375587.8	NP_001012267.1
ASPN	NM_017680.6	c.388-194T>C		intron_variant		ENST00000710274.1	NP_060150.4
ASPN	NM_001193335.3	c.388-194T>C		intron_variant			NP_001180264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPP	ENST00000375587.8	c.564+86906A>G		intron_variant		1	NM_001012267.3	ENSP00000364737	P1
ASPN	ENST00000375544.7	c.388-194T>C		intron_variant		1		ENSP00000364694	P1

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

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.367

Alfa AF: 0.306 Hom.: 7505

Bravo AF: 0.386

Asia WGS AF: 0.148 AC: 516 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs13301537; hg19: chr9-95229047;