Genetic Variant BGN:c.*520C>A (chrX-153508965-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001711.6(BGN):c.*520C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 125,454 control chromosomes in the GnomAD database, including 5,618 homozygotes. There are 9,264 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 4737 hom., 8271 hem., cov: 21)

Exomes 𝑓: 0.30 ( 881 hom. 993 hem. )

Consequence

BGN
NM_001711.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

5 publications found

Variant links:

Genes affected

BGN (HGNC:1044): (biglycan) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues. This protein may also regulate inflammation and innate immunity. Additionally, the encoded protein may contribute to atherosclerosis and aortic valve stenosis in human patients. This gene and the related gene decorin are thought to be the result of a gene duplication. [provided by RefSeq, Nov 2015]

BGN Gene-Disease associations (from GenCC):

Meester-Loeys syndrome
Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Illumina, G2P
X-linked spondyloepimetaphyseal dysplasia
Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

BGN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6 link	c.*520C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000331595.9	NP_001702.1	P21810B4DNL4
BGN	XM_017029724.3 link	c.*520C>A		3_prime_UTR_variant	Exon 7 of 7		XP_016885213.1	P21810

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BGN	ENST00000331595.9 link	c.*520C>A	3_prime_UTR_variant	Exon 8 of 8	1	NM_001711.6	ENSP00000327336.4	P21810
BGN	ENST00000472615.5 link	n.1644C>A	non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000480756.1 link	n.1697C>A	non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000492658.1 link	n.*160C>A	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

32154

AN:

108127

Hom.:

4737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.0685

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.289

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.303

AC:

5231

AN:

17277

Hom.:

881

Cov.:

AF XY:

0.305

AC XY:

993

AN XY:

3259

show subpopulations

African (AFR)

AF:

0.0635

AC:

AN:

378

American (AMR)

AF:

0.121

AC:

152

AN:

1253

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

105

AN:

386

East Asian (EAS)

AF:

0.0380

AC:

AN:

368

South Asian (SAS)

AF:

0.149

AC:

240

AN:

1613

European-Finnish (FIN)

AF:

0.392

AC:

334

AN:

851

Middle Eastern (MID)

AF:

0.239

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

4028

AN:

11291

Other (OTH)

AF:

0.299

AC:

312

AN:

1045

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

117

234

352

469

586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.297

AC:

32145

AN:

108177

Hom.:

4737

Cov.:

AF XY:

0.270

AC XY:

8271

AN XY:

30673

show subpopulations

African (AFR)

AF:

0.0882

AC:

2652

AN:

30085

American (AMR)

AF:

0.214

AC:

2192

AN:

10249

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

884

AN:

2592

East Asian (EAS)

AF:

0.0690

AC:

240

AN:

3476

South Asian (SAS)

AF:

0.184

AC:

455

AN:

2477

European-Finnish (FIN)

AF:

0.448

AC:

2403

AN:

5366

Middle Eastern (MID)

AF:

0.290

AC:

AN:

207

European-Non Finnish (NFE)

AF:

0.439

AC:

22629

AN:

51583

Other (OTH)

AF:

0.269

AC:

398

AN:

1481

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

688

1377

2065

2754

3442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.404

Hom.:

4654

Bravo

AF:

0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.079

(source)

DANN

Benign

0.50

PhyloP100

-1.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over