Genetic Variant BGN:c.*842A>G (chrX-153509287-A-G) – 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.*842A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.98 ( 37498 hom., 31294 hem., cov: 22)

Exomes 𝑓: 1.0 ( 186 hom. 261 hem. )

Failed GnomAD Quality Control

Consequence

BGN
NM_001711.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

3 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=-0.89).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6 link	c.*842A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3 link	c.*842A>G		3_prime_UTR_variant	Exon 7 of 7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
BGN	ENST00000331595.9 link	c.*842A>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000472615.5 link	n.1966A>G	non_coding_transcript_exon_variant	Exon 8 of 8	5
BGN	ENST00000480756.1 link	n.2019A>G	non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.982

AC:

107601

AN:

109580

Hom.:

37505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.988

GnomAD4 exome

AF:

1.00

AC:

633

AN:

633

Hom.:

186

Cov.:

AF XY:

1.00

AC XY:

261

AN XY:

261

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

496

AN:

496

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.982

AC:

107643

AN:

109632

Hom.:

37498

Cov.:

AF XY:

0.982

AC XY:

31294

AN XY:

31854

show subpopulations

African (AFR)

AF:

0.936

AC:

28102

AN:

30010

American (AMR)

AF:

0.995

AC:

10237

AN:

10285

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

2633

AN:

2633

East Asian (EAS)

AF:

1.00

AC:

3472

AN:

3472

South Asian (SAS)

AF:

1.00

AC:

2540

AN:

2541

European-Finnish (FIN)

AF:

1.00

AC:

5735

AN:

5735

Middle Eastern (MID)

AF:

1.00

AC:

218

AN:

218

European-Non Finnish (NFE)

AF:

1.00

AC:

52545

AN:

52559

Other (OTH)

AF:

0.988

AC:

1479

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

129

193

258

322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.989

Hom.:

8526

Bravo

AF:

0.980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

(source)

DANN

Benign

0.40

PhyloP100

-1.2

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