X-153504659-C-T

Variant names:

• chrX-153504659-C-T
• NM_001711.6:c.28C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001711.6(BGN):​c.28C>T​(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,096,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000010 (0 hom. 5 hem.)
• Consequence: BGN NM_001711.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-153504659-C-T is Benign according to our data. Variant chrX-153504659-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2564952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.68 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 11 XL,AD gene.

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.28C>T	p.Leu10Leu	synonymous	Exon 2 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.28C>T	p.Leu10Leu	synonymous	Exon 2 of 8	ENSP00000327336.4	P21810
	BGN	ENST00000859737.1		c.28C>T	p.Leu10Leu	synonymous	Exon 2 of 8	ENSP00000529796.1
	BGN	ENST00000859739.1		c.28C>T	p.Leu10Leu	synonymous	Exon 2 of 8	ENSP00000529798.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1096116 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 361796

African (AFR) AF: 0.00 AC: 0 AN: 26383

American (AMR) AF: 0.00 AC: 0 AN: 35146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30153

South Asian (SAS) AF: 0.00 AC: 0 AN: 54033

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40189

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.0000119 AC: 10 AN: 840738

Other (OTH) AF: 0.0000217 AC: 1 AN: 46026

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		1.7

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

hg19: chrX-152770117;