Variant X-153504652-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001711.6(BGN):c.21C>A(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,730 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

BGN
NM_001711.6 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.61

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:

BGN (HGNC:):

BGN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-2.61 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BGN	NM_001711.6 linkuse as main transcript	c.21C>A	p.Leu7Leu	synonymous_variant	2/8	ENST00000331595.9	NP_001702.1	P21810B4DNL4
BGN	XM_017029724.3 linkuse as main transcript	c.21C>A	p.Leu7Leu	synonymous_variant	1/7		XP_016885213.1	P21810

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BGN	ENST00000331595.9 linkuse as main transcript	c.21C>A	p.Leu7Leu	synonymous_variant	2/8	1	NM_001711.6	ENSP00000327336.4	P21810
BGN	ENST00000431891.1 linkuse as main transcript	c.21C>A	p.Leu7Leu	synonymous_variant	2/5	5		ENSP00000402525.1	C9JKG1
BGN	ENST00000472615.5 linkuse as main transcript	n.165C>A		non_coding_transcript_exon_variant	2/8	5
BGN	ENST00000480756.1 linkuse as main transcript	n.163C>A		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.14e-7

AC:

AN:

1093730

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BGN-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 07, 2023

The BGN c.21C>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to create a cryptic splice acceptor site (Alamut Visual Plus v1.6.1). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.29

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over