chrX-153506051-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001711.6(BGN):c.540C>T(p.Ser180Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,208,518 control chromosomes in the GnomAD database, including 86,306 homozygotes. There are 179,722 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 6137 hom., 12295 hem., cov: 23)

Exomes 𝑓: 0.46 ( 80169 hom. 167427 hem. )

Consequence

BGN
NM_001711.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -6.58

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-153506051-C-T is Benign according to our data. Variant chrX-153506051-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6 link	c.540C>T	p.Ser180Ser	synonymous_variant	Exon 4 of 8	ENST00000331595.9	NP_001702.1	P21810B4DNL4
BGN	XM_017029724.3 link	c.540C>T	p.Ser180Ser	synonymous_variant	Exon 3 of 7		XP_016885213.1	P21810

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9 link	c.540C>T	p.Ser180Ser	synonymous_variant	Exon 4 of 8	1	NM_001711.6	ENSP00000327336.4		P21810

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

41275

AN:

111200

Hom.:

6140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.426

AC:

77501

AN:

181856

AF XY:

0.434

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.378

Gnomad ASJ exome

AF:

0.387

Gnomad EAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.479

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.462

AC:

507411

AN:

1097267

Hom.:

80169

Cov.:

AF XY:

0.462

AC XY:

167427

AN XY:

362771

show subpopulations

African (AFR)

AF:

0.145

AC:

3828

AN:

26391

American (AMR)

AF:

0.375

AC:

13182

AN:

35142

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

7639

AN:

19380

East Asian (EAS)

AF:

0.387

AC:

11680

AN:

30195

South Asian (SAS)

AF:

0.410

AC:

22208

AN:

54125

European-Finnish (FIN)

AF:

0.461

AC:

18556

AN:

40217

Middle Eastern (MID)

AF:

0.437

AC:

1809

AN:

4135

European-Non Finnish (NFE)

AF:

0.485

AC:

408120

AN:

841617

Other (OTH)

AF:

0.443

AC:

20389

AN:

46065

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10776

21552

32327

43103

53879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13194

26388

39582

52776

65970

<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:

0.371

AC:

41262

AN:

111251

Hom.:

6137

Cov.:

AF XY:

0.367

AC XY:

12295

AN XY:

33477

show subpopulations

African (AFR)

AF:

0.154

AC:

4733

AN:

30766

American (AMR)

AF:

0.395

AC:

4185

AN:

10605

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1039

AN:

2641

East Asian (EAS)

AF:

0.428

AC:

1491

AN:

3487

South Asian (SAS)

AF:

0.387

AC:

1006

AN:

2602

European-Finnish (FIN)

AF:

0.452

AC:

2686

AN:

5947

Middle Eastern (MID)

AF:

0.512

AC:

111

AN:

217

European-Non Finnish (NFE)

AF:

0.478

AC:

25213

AN:

52798

Other (OTH)

AF:

0.368

AC:

557

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

884

1768

2652

3536

4420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.443

Hom.:

32302

Bravo

AF:

0.359

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25173489) -

not specified

Benign:1

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

X-linked spondyloepimetaphyseal dysplasia

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meester-Loeys syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

(source)

DANN

Benign

0.81

PhyloP100

-6.6

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over