X-153509287-A-G

Variant names:

• chrX-153509287-A-G
• rs2980054
• NM_001711.6:c.*842A>G

Variant summary

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

The NM_001711.6(BGN):​c.*842A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.98 (37498 hom., 31294 hem., cov: 22)
  • Exomes 𝑓: 1.0 (186 hom. 261 hem.)
  • Failed GnomAD Quality Control
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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: Illumina, Genomics England PanelApp, Ambry Genetics, G2P
• X-linked spondyloepimetaphyseal dysplasia

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

  Inheritance: Unknown 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=-0.89).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 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.*842A>G		3_prime_UTR	Exon 8 of 8	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.*842A>G		3_prime_UTR	Exon 8 of 8	ENSP00000327336.4	P21810
	BGN	ENST00000859737.1		c.*842A>G		3_prime_UTR	Exon 8 of 8	ENSP00000529796.1
	BGN	ENST00000859739.1		c.*842A>G		3_prime_UTR	Exon 8 of 8	ENSP00000529798.1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 107601 AN: 109580 Hom.: 37505 Cov.: 22

Gnomad AFR AF: 0.937

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

GnomAD4 exome AF: 1.00 AC: 633 AN: 633 Hom.: 186 Cov.: 0 AF XY: 1.00 AC XY: 261 AN XY: 261

African (AFR) AF: 1.00 AC: 7 AN: 7

American (AMR) AF: 1.00 AC: 6 AN: 6

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 8 AN: 8

East Asian (EAS) AF: 1.00 AC: 14 AN: 14

South Asian (SAS) AF: 1.00 AC: 52 AN: 52

European-Finnish (FIN) AF: 1.00 AC: 19 AN: 19

Middle Eastern (MID) AF: 1.00 AC: 7 AN: 7

European-Non Finnish (NFE) AF: 1.00 AC: 496 AN: 496

Other (OTH) AF: 1.00 AC: 24 AN: 24

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.982 AC: 107643 AN: 109632 Hom.: 37498 Cov.: 22 AF XY: 0.982 AC XY: 31294 AN XY: 31854

African (AFR) AF: 0.936 AC: 28102 AN: 30010

American (AMR) AF: 0.995 AC: 10237 AN: 10285

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2633 AN: 2633

East Asian (EAS) AF: 1.00 AC: 3472 AN: 3472

South Asian (SAS) AF: 1.00 AC: 2540 AN: 2541

European-Finnish (FIN) AF: 1.00 AC: 5735 AN: 5735

Middle Eastern (MID) AF: 1.00 AC: 218 AN: 218

European-Non Finnish (NFE) AF: 1.00 AC: 52545 AN: 52559

Other (OTH) AF: 0.988 AC: 1479 AN: 1497

Alfa AF: 0.989 Hom.: 8526

Bravo AF: 0.980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.40
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2980054;

hg19: chrX-152774745;