X-153506051-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1166521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153506051-C-T is described in Lovd as [Benign]. Variant chrX-153506051-C-T is described in Lovd as [Likely_benign].

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.:

AF XY:

0.368

AC XY:

12294

AN XY:

33416

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

GnomAD3 exomes

AF:

0.426

AC:

77501

AN:

181856

Hom.:

10792

AF XY:

0.434

AC XY:

28910

AN XY:

66544

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 SAS exome

AF:

0.414

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

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.375

Gnomad4 ASJ exome

AF:

0.394

Gnomad4 EAS exome

AF:

0.387

Gnomad4 SAS exome

AF:

0.410

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.371

AC:

41262

AN:

111251

Hom.:

6137

Cov.:

AF XY:

0.367

AC XY:

12295

AN XY:

33477

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.456

Hom.:

25247

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

DANN

Benign

0.81

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

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