rs2073479

Variant names:

• chrX-153507015-C-T
• rs2073479
• NM_001711.6:c.771-32C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153507015-C-T
• chrX-153507015-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001711.6(BGN):​c.771-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,206,060 control chromosomes in the GnomAD database, including 61,626 homozygotes. There are 152,180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (5326 hom., 12083 hem., cov: 23)
  • Exomes 𝑓: 0.39 (56300 hom. 140097 hem.)
• Consequence: BGN NM_001711.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.301
• Publications: 9 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: Genomics England PanelApp, Illumina, Ambry Genetics, G2P
• X-linked spondyloepimetaphyseal dysplasia

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-153507015-C-T is Benign according to our data. Variant chrX-153507015-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BGN	NM_001711.6	MANE Select	c.771-32C>T		intron	N/A	NP_001702.1	P21810

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BGN	ENST00000331595.9	TSL:1 MANE Select	c.771-32C>T		intron	N/A	ENSP00000327336.4	P21810
	BGN	ENST00000859737.1		c.822-32C>T		intron	N/A	ENSP00000529796.1
	BGN	ENST00000859739.1		c.822-32C>T		intron	N/A	ENSP00000529798.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 40363 AN: 111487 Hom.: 5321 Cov.: 23

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.389

GnomAD2 exomes AF: 0.408 AC: 73507 AN: 180058 AF XY: 0.402

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.472

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.388 AC: 425070 AN: 1094521 Hom.: 56300 Cov.: 34 AF XY: 0.389 AC XY: 140097 AN XY: 360359

African (AFR) AF: 0.263 AC: 6941 AN: 26353

American (AMR) AF: 0.560 AC: 19556 AN: 34950

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 8975 AN: 19346

East Asian (EAS) AF: 0.508 AC: 15284 AN: 30089

South Asian (SAS) AF: 0.402 AC: 21727 AN: 54012

European-Finnish (FIN) AF: 0.393 AC: 15842 AN: 40326

Middle Eastern (MID) AF: 0.460 AC: 1901 AN: 4130

European-Non Finnish (NFE) AF: 0.377 AC: 316669 AN: 839386

Other (OTH) AF: 0.396 AC: 18175 AN: 45929

GnomAD4 genome AF: 0.362 AC: 40387 AN: 111539 Hom.: 5326 Cov.: 23 AF XY: 0.358 AC XY: 12083 AN XY: 33779

African (AFR) AF: 0.259 AC: 7966 AN: 30726

American (AMR) AF: 0.483 AC: 5132 AN: 10623

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1228 AN: 2636

East Asian (EAS) AF: 0.453 AC: 1587 AN: 3501

South Asian (SAS) AF: 0.384 AC: 1036 AN: 2695

European-Finnish (FIN) AF: 0.389 AC: 2348 AN: 6037

Middle Eastern (MID) AF: 0.372 AC: 80 AN: 215

European-Non Finnish (NFE) AF: 0.380 AC: 20120 AN: 52915

Other (OTH) AF: 0.397 AC: 603 AN: 1517

Alfa AF: 0.382 Hom.: 12550

Bravo AF: 0.374

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Meester-Loeys syndrome (1)
-	-	1	X-linked spondyloepimetaphyseal dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.80
PhyloP100		0.30
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: rs2073479; hg19: chrX-152772473; COSMIC: COSV59036377; COSMIC: COSV59036377;