X-153508763-G-T

Variant names:

• chrX-153508763-G-T
• rs743642
• NM_001711.6:c.*318G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001711.6(BGN):​c.*318G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 344,255 control chromosomes in the GnomAD database, including 5,549 homozygotes. There are 17,203 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 0.21 (2727 hom., 7112 hem., cov: 23)
  • Exomes 𝑓: 0.15 (2822 hom. 10091 hem.)
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BGN	NM_001711.6	MANE Select	c.*318G>T		3_prime_UTR	Exon 8 of 8	NP_001702.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BGN	ENST00000331595.9	TSL:1 MANE Select	c.*318G>T		3_prime_UTR	Exon 8 of 8	ENSP00000327336.4
	BGN	ENST00000859737.1		c.*318G>T		3_prime_UTR	Exon 8 of 8	ENSP00000529796.1
	BGN	ENST00000859739.1		c.*318G>T		3_prime_UTR	Exon 8 of 8	ENSP00000529798.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 23710 AN: 111297 Hom.: 2723 Cov.: 23

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.145 AC: 33827 AN: 232904 Hom.: 2822 Cov.: 0 AF XY: 0.160 AC XY: 10091 AN XY: 63074

African (AFR) AF: 0.387 AC: 2888 AN: 7464

American (AMR) AF: 0.457 AC: 4174 AN: 9139

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 270 AN: 7162

East Asian (EAS) AF: 0.305 AC: 4577 AN: 14994

South Asian (SAS) AF: 0.267 AC: 5567 AN: 20847

European-Finnish (FIN) AF: 0.0909 AC: 1376 AN: 15145

Middle Eastern (MID) AF: 0.129 AC: 126 AN: 973

European-Non Finnish (NFE) AF: 0.0876 AC: 12521 AN: 142979

Other (OTH) AF: 0.164 AC: 2328 AN: 14201

GnomAD4 genome AF: 0.213 AC: 23724 AN: 111351 Hom.: 2727 Cov.: 23 AF XY: 0.212 AC XY: 7112 AN XY: 33583

African (AFR) AF: 0.389 AC: 11867 AN: 30496

American (AMR) AF: 0.406 AC: 4283 AN: 10562

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 95 AN: 2642

East Asian (EAS) AF: 0.347 AC: 1211 AN: 3493

South Asian (SAS) AF: 0.261 AC: 692 AN: 2651

European-Finnish (FIN) AF: 0.0909 AC: 555 AN: 6108

Middle Eastern (MID) AF: 0.138 AC: 30 AN: 217

European-Non Finnish (NFE) AF: 0.0846 AC: 4484 AN: 52972

Other (OTH) AF: 0.236 AC: 361 AN: 1531

Alfa AF: 0.139 Hom.: 8705

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.62
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743642; hg19: chrX-152774221;