Variant 9-92474742-C-CTCATCA 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_156insTGATGA(p.Asp50_Asp51dup) variant causes a inframe insertion change. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 444 hom., cov: 0)

Exomes 𝑓: 0.073 ( 2003 hom. )

Consequence

ASPN
ENST00000375544.7 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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-CTCATCA is Benign according to our data. Variant chr9-92474742-C-CTCATCA is described in ClinVar as [Benign]. Clinvar id is 1237100.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASPN	NM_017680.6 linkuse as main transcript	c.155_156insTGATGA	p.Asp50_Asp51dup	inframe_insertion	2/8	ENST00000710274.1	NP_060150.4
ASPN	NM_001193335.3 linkuse as main transcript	c.155_156insTGATGA	p.Asp50_Asp51dup	inframe_insertion	2/6		NP_001180264.1
CENPP	NM_001012267.3 linkuse as main transcript	c.564+94922_564+94927dup		intron_variant		ENST00000375587.8	NP_001012267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPN	ENST00000375544.7 linkuse as main transcript	c.155_156insTGATGA	p.Asp50_Asp51dup	inframe_insertion	2/8	1		ENSP00000364694	P1
CENPP	ENST00000375587.8 linkuse as main transcript	c.564+94922_564+94927dup		intron_variant		1	NM_001012267.3	ENSP00000364737	P1	Q6IPU0-1

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

10723

AN:

147504

Hom.:

444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.0490

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.0502

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0645

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0744

GnomAD4 exome

AF:

0.0728

AC:

100838

AN:

1385086

Hom.:

2003

Cov.:

AF XY:

0.0713

AC XY:

49141

AN XY:

689672

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.0625

Gnomad4 ASJ exome

AF:

0.0683

Gnomad4 EAS exome

AF:

0.0700

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.0668

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.0647

GnomAD4 genome

AF:

0.0727

AC:

10735

AN:

147610

Hom.:

444

Cov.:

AF XY:

0.0717

AC XY:

5144

AN XY:

71758

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.0654

Gnomad4 ASJ

AF:

0.0717

Gnomad4 EAS

AF:

0.0505

Gnomad4 SAS

AF:

0.0278

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.0757

Gnomad4 OTH

AF:

0.0726

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 05, 2021

Reported in 3.1% of alleles of patients with developmental hip dysplasia in the Han Chinese population, but also seen in 3.4% of alleles of control samples, which was not a statistically significant difference (Shi et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; The D15 allele is described as a possible risk allele associated with knee osteoarthritis in the Greek population however, this finding was not statistically significant (Kaliakatsos et al., 2006); Among Han Chinese patients with ankylosing spondylitis the frequency of the D15 allele was the same as in controls (Liu et al., 2010); In-frame duplication of 2 Aspartate residues, which results in an allele with 15 Aspartate residues, or a D15 allele; This variant is associated with the following publications: (PMID: 21329514, 16377215, 20144272, 29233086) -

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