Variant 9-92474742-C-CTCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000375544.7(ASPN):c.155_156insTGA(p.Asp51dup) variant causes a inframe insertion change. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 6793 hom., cov: 0)

Exomes 𝑓: 0.19 ( 13869 hom. )

Consequence

ASPN
ENST00000375544.7 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2O:2

Conservation

PhyloP100: 4.52

Variant links:

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]

ASPN links:

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]

CENPP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 9-92474742-C-CTCA is Benign according to our data. Variant chr9-92474742-C-CTCA is described in ClinVar as [Benign]. Clinvar id is 2527.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASPN	NM_017680.6 linkuse as main transcript	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/8	ENST00000710274.1
ASPN	NM_001193335.3 linkuse as main transcript	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/6
CENPP	NM_001012267.3 linkuse as main transcript	c.564+94925_564+94927dup		intron_variant		ENST00000375587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPN	ENST00000375544.7 linkuse as main transcript	c.155_156insTGA	p.Asp51dup	inframe_insertion	2/8	1		P1
CENPP	ENST00000375587.8 linkuse as main transcript	c.564+94925_564+94927dup		intron_variant		1	NM_001012267.3	P1	Q6IPU0-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

39967

AN:

147386

Hom.:

6790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.192

AC:

265438

AN:

1383238

Hom.:

13869

Cov.:

AF XY:

0.191

AC XY:

131736

AN XY:

688804

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.0380

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.271

AC:

39995

AN:

147490

Hom.:

6793

Cov.:

AF XY:

0.265

AC XY:

18973

AN XY:

71698

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.0335

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.247

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Mar 19, 2020

- -

CENPP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Osteoarthritis susceptibility 3

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Lumbar disk degeneration, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over