Variant 15-88859008-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001369268.1(ACAN):c.6423T>C(p.Leu2141Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,613,796 control chromosomes in the GnomAD database, including 486,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47112 hom., cov: 32)

Exomes 𝑓: 0.77 ( 439201 hom. )

Consequence

ACAN
NM_001369268.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.81

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 15-88859008-T-C is Benign according to our data. Variant chr15-88859008-T-C is described in ClinVar as [Benign]. Clinvar id is 1188994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-88859008-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAN	NM_001369268.1 linkuse as main transcript	c.6423T>C	p.Leu2141Leu	synonymous_variant	12/19	ENST00000560601.4	NP_001356197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAN	ENST00000560601.4 linkuse as main transcript	c.6423T>C	p.Leu2141Leu	synonymous_variant	12/19	3	NM_001369268.1	ENSP00000453581.2		H0YMF1

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119292

AN:

152052

Hom.:

47083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.849

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.786

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.785

GnomAD3 exomes

AF:

0.730

AC:

181887

AN:

249080

Hom.:

67644

AF XY:

0.733

AC XY:

99039

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.851

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.787

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.713

Gnomad NFE exome

AF:

0.795

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.772

AC:

1128855

AN:

1461626

Hom.:

439201

Cov.:

AF XY:

0.770

AC XY:

559774

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.848

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.785

Gnomad4 EAS exome

AF:

0.537

Gnomad4 SAS exome

AF:

0.682

Gnomad4 FIN exome

AF:

0.710

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.768

GnomAD4 genome

AF:

0.784

AC:

119371

AN:

152170

Hom.:

47112

Cov.:

AF XY:

0.774

AC XY:

57600

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.848

Gnomad4 AMR

AF:

0.699

Gnomad4 ASJ

AF:

0.786

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.717

Gnomad4 NFE

AF:

0.797

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.789

Hom.:

71051

Bravo

AF:

0.782

Asia WGS

AF:

0.676

AC:

2352

AN:

3478

EpiCase

AF:

0.794

EpiControl

AF:

0.800

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-1.0

CADD

Benign

0.11

DANN

Benign

0.28

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