rs199928539

Variant names:

• chrX-153504652-C-A
• NM_001711.6:c.21C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153504652-C-A
• chrX-153504652-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.61

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]

ACMG classification

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 rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.21C>A	p.Leu7Leu	synonymous_variant	Exon 2 of 8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.21C>A	p.Leu7Leu	synonymous_variant	Exon 1 of 7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.21C>A	p.Leu7Leu	synonymous_variant	Exon 2 of 8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000431891.1	c.21C>A	p.Leu7Leu	synonymous_variant	Exon 2 of 5	5		ENSP00000402525.1
BGN	ENST00000472615.5	n.165C>A		non_coding_transcript_exon_variant	Exon 2 of 8	5
BGN	ENST00000480756.1	n.163C>A		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1093730 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1 AN XY: 359784

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.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BGN-related disorder Uncertain:1

Apr 07, 2023

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Other links and lift over

hg19: chrX-152770110;