X-153507015-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001711.6(BGN):c.771-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,206,060 control chromosomes in the GnomAD database, including 61,626 homozygotes. There are 152,180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 5326 hom., 12083 hem., cov: 23)

Exomes 𝑓: 0.39 ( 56300 hom. 140097 hem. )

Consequence

BGN
NM_001711.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.301

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-153507015-C-T is Benign according to our data. Variant chrX-153507015-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6 link	c.771-32C>T		intron_variant	Intron 6 of 7	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3 link	c.771-32C>T		intron_variant	Intron 5 of 6		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
BGN	ENST00000331595.9 link	c.771-32C>T	intron_variant	Intron 6 of 7	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000472615.5 link	n.788-32C>T	intron_variant	Intron 6 of 7	5
BGN	ENST00000480756.1 link	n.841-32C>T	intron_variant	Intron 6 of 7	5
BGN	ENST00000492658.1 link	n.294+401C>T	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

40363

AN:

111487

Hom.:

5321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.403

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.389

GnomAD2 exomes

AF:

0.408

AC:

73507

AN:

180058

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.388

AC:

425070

AN:

1094521

Hom.:

56300

Cov.:

AF XY:

0.389

AC XY:

140097

AN XY:

360359

show subpopulations

African (AFR)

AF:

0.263

AC:

6941

AN:

26353

American (AMR)

AF:

0.560

AC:

19556

AN:

34950

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

8975

AN:

19346

East Asian (EAS)

AF:

0.508

AC:

15284

AN:

30089

South Asian (SAS)

AF:

0.402

AC:

21727

AN:

54012

European-Finnish (FIN)

AF:

0.393

AC:

15842

AN:

40326

Middle Eastern (MID)

AF:

0.460

AC:

1901

AN:

4130

European-Non Finnish (NFE)

AF:

0.377

AC:

316669

AN:

839386

Other (OTH)

AF:

0.396

AC:

18175

AN:

45929

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9750

19499

29249

38998

48748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10906

21812

32718

43624

54530

<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:

0.362

AC:

40387

AN:

111539

Hom.:

5326

Cov.:

AF XY:

0.358

AC XY:

12083

AN XY:

33779

show subpopulations

African (AFR)

AF:

0.259

AC:

7966

AN:

30726

American (AMR)

AF:

0.483

AC:

5132

AN:

10623

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1228

AN:

2636

East Asian (EAS)

AF:

0.453

AC:

1587

AN:

3501

South Asian (SAS)

AF:

0.384

AC:

1036

AN:

2695

European-Finnish (FIN)

AF:

0.389

AC:

2348

AN:

6037

Middle Eastern (MID)

AF:

0.372

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.380

AC:

20120

AN:

52915

Other (OTH)

AF:

0.397

AC:

603

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

933

1867

2800

3734

4667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.382

Hom.:

12550

Bravo

AF:

0.374

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 04, 2018

GeneDx

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.9

(source)

DANN

Benign

0.80

PhyloP100

0.30

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over