X-153504944-A-G

Variant names:

• chrX-153504944-A-G
• rs2980053
• NM_001711.6:c.238+75A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001711.6(BGN):​c.238+75A>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 0.87 (29971 hom., 29085 hem., cov: 23)
  • Exomes 𝑓: 0.94 (280115 hom. 253510 hem.)
  • Failed GnomAD Quality Control
• Consequence: BGN NM_001711.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.345
• Publications: 7 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=-0.9).
• BP6: Variant X-153504944-A-G is Benign according to our data. Variant chrX-153504944-A-G is described in ClinVar as Benign. ClinVar VariationId is 1192382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.238+75A>G		intron_variant	Intron 2 of 7	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.238+75A>G		intron_variant	Intron 1 of 6		XP_016885213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9	c.238+75A>G		intron_variant	Intron 2 of 7	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000431891.1	c.238+75A>G		intron_variant	Intron 2 of 4	5		ENSP00000402525.1
BGN	ENST00000472615.5	n.382+75A>G		intron_variant	Intron 2 of 7	5
BGN	ENST00000480756.1	n.329+126A>G		intron_variant	Intron 2 of 7	5

Frequencies

GnomAD3 genomes AF: 0.872 AC: 96724 AN: 110882 Hom.: 29975 Cov.: 23

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.954

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.876

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.936 AC: 852460 AN: 911124 Hom.: 280115 AF XY: 0.942 AC XY: 253510 AN XY: 269218

African (AFR) AF: 0.694 AC: 15476 AN: 22302

American (AMR) AF: 0.969 AC: 30030 AN: 30999

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 14299 AN: 15671

East Asian (EAS) AF: 0.924 AC: 26927 AN: 29153

South Asian (SAS) AF: 0.953 AC: 43323 AN: 45447

European-Finnish (FIN) AF: 0.963 AC: 27459 AN: 28508

Middle Eastern (MID) AF: 0.953 AC: 2580 AN: 2708

European-Non Finnish (NFE) AF: 0.941 AC: 655611 AN: 696587

Other (OTH) AF: 0.925 AC: 36755 AN: 39749

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.872 AC: 96756 AN: 110934 Hom.: 29971 Cov.: 23 AF XY: 0.877 AC XY: 29085 AN XY: 33150

African (AFR) AF: 0.692 AC: 21061 AN: 30415

American (AMR) AF: 0.937 AC: 9914 AN: 10580

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 2420 AN: 2636

East Asian (EAS) AF: 0.920 AC: 3200 AN: 3478

South Asian (SAS) AF: 0.959 AC: 2459 AN: 2565

European-Finnish (FIN) AF: 0.966 AC: 5766 AN: 5967

Middle Eastern (MID) AF: 0.954 AC: 207 AN: 217

European-Non Finnish (NFE) AF: 0.940 AC: 49728 AN: 52882

Other (OTH) AF: 0.878 AC: 1329 AN: 1514

Alfa AF: 0.846 Hom.: 3502

Bravo AF: 0.864

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

X-linked spondyloepimetaphyseal dysplasia Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meester-Loeys syndrome Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.43
PhyloP100		-0.34
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: rs2980053; hg19: chrX-152770402;