Variant rs2351491 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001369268.1(ACAN):c.2289C>T(p.Pro763=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,494,474 control chromosomes in the GnomAD database, including 270,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20173 hom., cov: 33)

Exomes 𝑓: 0.60 ( 250780 hom. )

Consequence

ACAN
NM_001369268.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.817

Variant links:

Genes affected

ACAN (HGNC:319): (aggrecan) This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]

ACAN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 15-88854874-C-T is Benign according to our data. Variant chr15-88854874-C-T is described in ClinVar as [Benign]. Clinvar id is 1181962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-88854874-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.817 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1 linkuse as main transcript	c.2289C>T	p.Pro763=	synonymous_variant	12/19	ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4 linkuse as main transcript	c.2289C>T	p.Pro763=	synonymous_variant	12/19	3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73335

AN:

151986

Hom.:

20175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.519

GnomAD3 exomes

AF:

0.504

AC:

80915

AN:

160402

Hom.:

22906

AF XY:

0.519

AC XY:

44677

AN XY:

86082

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.640

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.600

AC:

805043

AN:

1342370

Hom.:

250780

Cov.:

AF XY:

0.597

AC XY:

392611

AN XY:

657470

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

0.646

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.482

AC:

73330

AN:

152104

Hom.:

20173

Cov.:

AF XY:

0.475

AC XY:

35305

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.596

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.598

Hom.:

43683

Bravo

AF:

0.457

Asia WGS

AF:

0.333

AC:

1158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondyloepimetaphyseal dysplasia, aggrecan type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Osteochondritis dissecans

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Spondyloepiphyseal dysplasia, Kimberley type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.5

DANN

Benign

0.44

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.

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