9-92474742-CTCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001193335.3(ASPN):c.153_155del(p.Asp51del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.439 in 1,532,104 control chromosomes in the GnomAD database, including 124,043 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13265 hom., cov: 0)
  • Exomes 𝑓: 0.44 (110778 hom.)
• Consequence: ASPN NM_001193335.3 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.52

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-92474742-CTCA-C is Benign according to our data. Variant chr9-92474742-CTCA-C is described in ClinVar as [Benign]. Clinvar id is 1302755.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92474742-CTCA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPN	NM_017680.6	c.153_155del	p.Asp51del	inframe_deletion	2/8	ENST00000710274.1
ASPN	NM_001193335.3	c.153_155del	p.Asp51del	inframe_deletion	2/6
CENPP	NM_001012267.3	c.564+94925_564+94927del		intron_variant		ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPN	ENST00000375544.7	c.153_155del	p.Asp51del	inframe_deletion	2/8	1		P1
CENPP	ENST00000375587.8	c.564+94925_564+94927del		intron_variant		1	NM_001012267.3	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 58957 AN: 147384 Hom.: 13258 Cov.: 0

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.281

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.444 AC: 614369 AN: 1384612 Hom.: 110778 AF XY: 0.443 AC XY: 305192 AN XY: 689324

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.400 AC: 58985 AN: 147492 Hom.: 13265 Cov.: 0 AF XY: 0.405 AC XY: 29010 AN XY: 71690

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.412

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 11, 2021

This variant is associated with the following publications: (PMID: 21329514) -

Computational scores

Source: dbNSFP v4.3

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: rs3078372; hg19: chr9-95237024;