rs11538656

Positions:

• chrX-153508965-C-A
• chrX-153508965-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001711.6(BGN):​c.*520C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 125,454 control chromosomes in the GnomAD database, including 5,618 homozygotes. There are 9,264 hemizygotes in GnomAD. 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 0.30 (4737 hom., 8271 hem., cov: 21)
  • Exomes 𝑓: 0.30 (881 hom. 993 hem.)
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BGN	NM_001711.6	c.*520C>A		3_prime_UTR_variant	8/8	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.*520C>A		3_prime_UTR_variant	7/7		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.*520C>A		3_prime_UTR_variant	8/8	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000472615.5	n.1644C>A		non_coding_transcript_exon_variant	8/8	5
BGN	ENST00000480756.1	n.1697C>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 32154 AN: 108127 Hom.: 4737 Cov.: 21 AF XY: 0.270 AC XY: 8271 AN XY: 30613

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.289

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.303 AC: 5231 AN: 17277 Hom.: 881 Cov.: 0 AF XY: 0.305 AC XY: 993 AN XY: 3259

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.0380

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.297 AC: 32145 AN: 108177 Hom.: 4737 Cov.: 21 AF XY: 0.270 AC XY: 8271 AN XY: 30673

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.269

Alfa AF: 0.404 Hom.: 4654

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.079
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs11538656; hg19: chrX-152774423;