NM_001369268.1:c.-7-136G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001369268.1(ACAN):c.-7-136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 631,010 control chromosomes in the GnomAD database, including 114,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 26198 hom., cov: 32)

Exomes 𝑓: 0.60 ( 88617 hom. )

Consequence

ACAN
NM_001369268.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

ACAN-related short stature spectrum
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
osteochondritis dissecans
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
spondyloepiphyseal dysplasia, Kimberley type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
spondyloepimetaphyseal dysplasia, aggrecan type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
short stature-advanced bone age-early-onset osteoarthritis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACAN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 15-88836064-G-A is Benign according to our data. Variant chr15-88836064-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250552.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369268.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACAN	NM_001369268.1	MANE Select	c.-7-136G>A	intron	N/A	NP_001356197.1	P16112-4
ACAN	NM_001411097.1		c.-7-136G>A	intron	N/A	NP_001398026.1	A0A5K1VW97
ACAN	NM_013227.4		c.-7-136G>A	intron	N/A	NP_037359.3	P16112-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACAN	ENST00000560601.4	TSL:3 MANE Select	c.-7-136G>A	intron	N/A	ENSP00000453581.2	P16112-4
ACAN	ENST00000558207.5	TSL:1	c.-7-136G>A	intron	N/A	ENSP00000453003.1	Q6PID9
ACAN	ENST00000439576.7	TSL:5	c.-7-136G>A	intron	N/A	ENSP00000387356.2	P16112-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

88019

AN:

151914

Hom.:

26191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.597

AC:

286155

AN:

478978

Hom.:

88617

AF XY:

0.594

AC XY:

148630

AN XY:

250318

show subpopulations

African (AFR)

AF:

0.512

AC:

6610

AN:

12904

American (AMR)

AF:

0.548

AC:

11187

AN:

20410

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

8746

AN:

14294

East Asian (EAS)

AF:

0.233

AC:

7191

AN:

30846

South Asian (SAS)

AF:

0.499

AC:

21254

AN:

42620

European-Finnish (FIN)

AF:

0.659

AC:

27574

AN:

41864

Middle Eastern (MID)

AF:

0.695

AC:

1409

AN:

2028

European-Non Finnish (NFE)

AF:

0.647

AC:

185890

AN:

287302

Other (OTH)

AF:

0.610

AC:

16294

AN:

26710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5402

10805

16207

21610

27012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1174

2348

3522

4696

5870

<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:

0.579

AC:

88073

AN:

152032

Hom.:

26198

Cov.:

AF XY:

0.578

AC XY:

42926

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.503

AC:

20831

AN:

41448

American (AMR)

AF:

0.574

AC:

8772

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2144

AN:

3470

East Asian (EAS)

AF:

0.229

AC:

1179

AN:

5158

South Asian (SAS)

AF:

0.486

AC:

2342

AN:

4814

European-Finnish (FIN)

AF:

0.674

AC:

7132

AN:

10574

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.642

AC:

43619

AN:

67980

Other (OTH)

AF:

0.609

AC:

1284

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1905

3810

5715

7620

9525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.599

Hom.:

4679

Bravo

AF:

0.571

Asia WGS

AF:

0.418

AC:

1455

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.092

(source)

DANN

Benign

0.48

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over