X-153495074-G-T

Position:

• chrX-153495074-G-T

Variant summary

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

The NM_001711.6(BGN):​c.-51G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 108,973 control chromosomes in the GnomAD database, including 4,714 homozygotes. There are 9,480 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 0.31 (4708 hom., 9448 hem., cov: 21)
  • Exomes 𝑓: 0.45 (6 hom. 32 hem.)
• Consequence: BGN NM_001711.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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]

HAUS7 (HGNC:32979): (HAUS augmin like complex subunit 7) This gene encodes a subunit of the augmin complex, which regulates centrosome and mitotic spindle integrity, and is necessary for the completion of cytokinesis. The encoded protein was identified by interaction with ubiquitin C-terminal hydrolase 37. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

BGN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BGN	NM_001711.6	c.-51G>T		5_prime_UTR_variant	1/8	ENST00000331595.9	NP_001702.1
HAUS7	NM_001385483.1	c.-589+300C>A		intron_variant			NP_001372412.1
HAUS7	NR_073156.2	n.92+300C>A		intron_variant
HAUS7	NR_169631.1	n.92+300C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595	c.-51G>T		5_prime_UTR_variant	1/8	1	NM_001711.6	ENSP00000327336.4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 34203 AN: 108792 Hom.: 4709 Cov.: 21 AF XY: 0.303 AC XY: 9450 AN XY: 31224

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.448 AC: 60 AN: 134 Hom.: 6 Cov.: 0 AF XY: 0.471 AC XY: 32 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.314 AC: 34195 AN: 108839 Hom.: 4708 Cov.: 21 AF XY: 0.302 AC XY: 9448 AN XY: 31279

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.293

Alfa AF: 0.314 Hom.: 2683

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.0
DANN	Benign	0.88

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: rs5945197; hg19: chrX-152760532;