rs2980051

Variant names:

• chrX-153504296-A-G
• rs2980051
• NM_001711.6:c.-11-325A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001711.6(BGN):​c.-11-325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (10783 hom., 17147 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: BGN NM_001711.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26
• Publications: 3 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, Illumina, Genomics England PanelApp, G2P
• X-linked spondyloepimetaphyseal dysplasia

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

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-153504296-A-G is Benign according to our data. Variant chrX-153504296-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289069.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-11-325A>G		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.-11-325A>G		intron	N/A	ENSP00000327336.4	P21810
	BGN	ENST00000859737.1		c.-11-325A>G		intron	N/A	ENSP00000529796.1
	BGN	ENST00000859739.1		c.-11-325A>G		intron	N/A	ENSP00000529798.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 57160 AN: 111357 Hom.: 10787 Cov.: 24

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.515

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.513 AC: 57163 AN: 111413 Hom.: 10783 Cov.: 24 AF XY: 0.510 AC XY: 17147 AN XY: 33649

African (AFR) AF: 0.354 AC: 10863 AN: 30711

American (AMR) AF: 0.445 AC: 4731 AN: 10632

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1158 AN: 2642

East Asian (EAS) AF: 0.537 AC: 1864 AN: 3471

South Asian (SAS) AF: 0.583 AC: 1573 AN: 2700

European-Finnish (FIN) AF: 0.607 AC: 3625 AN: 5972

Middle Eastern (MID) AF: 0.553 AC: 121 AN: 219

European-Non Finnish (NFE) AF: 0.607 AC: 32079 AN: 52858

Other (OTH) AF: 0.468 AC: 716 AN: 1530

Alfa AF: 0.472 Hom.: 5639

Bravo AF: 0.490

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.41
PhyloP100		-2.3
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: rs2980051; hg19: chrX-152769754;