9-92460550-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The ENST00000375544.7(ASPN):ā€‹c.730T>Cā€‹(p.Leu244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000943 in 1,590,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000083 ( 0 hom. )

Consequence

ASPN
ENST00000375544.7 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.488
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 9-92460550-A-G is Benign according to our data. Variant chr9-92460550-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052688.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.488 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPNNM_017680.6 linkuse as main transcriptc.730T>C p.Leu244= synonymous_variant 6/8 ENST00000710274.1
CENPPNM_001012267.3 linkuse as main transcriptc.564+80691A>G intron_variant ENST00000375587.8
ASPNNM_001193335.3 linkuse as main transcriptc.713-3065T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPNENST00000375544.7 linkuse as main transcriptc.730T>C p.Leu244= synonymous_variant 6/81 P1
CENPPENST00000375587.8 linkuse as main transcriptc.564+80691A>G intron_variant 1 NM_001012267.3 P1Q6IPU0-1
ASPNENST00000375543.2 linkuse as main transcriptc.713-3065T>C intron_variant 2
ASPNENST00000650794.1 linkuse as main transcriptc.388-16T>C splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152264
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
250370
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000328
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000834
AC:
12
AN:
1438020
Hom.:
0
Cov.:
26
AF XY:
0.00000558
AC XY:
4
AN XY:
717018
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000550
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152382
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74524
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ASPN-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 20, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.5
DANN
Benign
0.74

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

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

Other links and lift over

dbSNP: rs539600204; hg19: chr9-95222832; API