Genetic Variant ENST00000375544.7:c.135_155delTGATGATGATGATGATGATGA (chr9-92474742-CTCATCATCATCATCATCATCA-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The ENST00000375544.7(ASPN):c.135_155delTGATGATGATGATGATGATGA(p.Asp45_Asp51del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000847 in 1,534,634 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

ASPN
ENST00000375544.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Publications

9 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000375544.7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPP	NM_001012267.3 link	c.564+94907_564+94927delATCATCATCATCATCATCATC		intron_variant	Intron 5 of 7	ENST00000375587.8	NP_001012267.1	Q6IPU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPN	ENST00000375544.7 link	c.135_155delTGATGATGATGATGATGATGA	p.Asp45_Asp51del	disruptive_inframe_deletion	Exon 2 of 8	1		ENSP00000364694.3		Q9BXN1
CENPP	ENST00000375587.8 link	c.564+94907_564+94927delATCATCATCATCATCATCATC		intron_variant	Intron 5 of 7	1	NM_001012267.3	ENSP00000364737.3		Q6IPU0-1

Frequencies

GnomAD3 genomes

AF:

0.00000678

AC:

AN:

147588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000865

AC:

AN:

1387046

Hom.:

AF XY:

0.00000869

AC XY:

AN XY:

690652

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30720

American (AMR)

AF:

0.0000730

AC:

AN:

41068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24902

East Asian (EAS)

AF:

0.00

AC:

AN:

37702

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81708

European-Finnish (FIN)

AF:

0.0000594

AC:

AN:

50526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00000378

AC:

AN:

1057302

Other (OTH)

AF:

0.0000174

AC:

AN:

57542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.579

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000678

AC:

AN:

147588

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39564

American (AMR)

AF:

0.00

AC:

AN:

14670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5002

South Asian (SAS)

AF:

0.00

AC:

AN:

4568

European-Finnish (FIN)

AF:

0.000100

AC:

AN:

9962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67178

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.5

Mutation Taster

=158/42

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over