X-153504944-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001711.6(BGN):​c.238+75A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 911,481 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000011 (0 hom. 0 hem.)
• Consequence: BGN NM_001711.6 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGN	NM_001711.6	c.238+75A>T		intron_variant	Intron 2 of 7	ENST00000331595.9	NP_001702.1
BGN	XM_017029724.3	c.238+75A>T		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>T		intron_variant	Intron 2 of 7	1	NM_001711.6	ENSP00000327336.4
BGN	ENST00000431891.1	c.238+75A>T		intron_variant	Intron 2 of 4	5		ENSP00000402525.1
BGN	ENST00000472615.5	n.382+75A>T		intron_variant	Intron 2 of 7	5
BGN	ENST00000480756.1	n.329+126A>T		intron_variant	Intron 2 of 7	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 911481 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 269299

African (AFR) AF: 0.00 AC: 0 AN: 22320

American (AMR) AF: 0.00 AC: 0 AN: 31003

Ashkenazi Jewish (ASJ) AF: 0.0000638 AC: 1 AN: 15671

East Asian (EAS) AF: 0.00 AC: 0 AN: 29155

South Asian (SAS) AF: 0.00 AC: 0 AN: 45454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28511

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 696889

Other (OTH) AF: 0.00 AC: 0 AN: 39768

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 3502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.56
PhyloP100		-0.34

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;