X-153504944-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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:3
• Conservation: PhyloP100: -0.345

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]

ACMG classification

Verdict is Benign. Variant got -16 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 id is 1192382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 29975 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BGN	NM_001711.6	c.238+75A>G		intron_variant		ENST00000331595.9
BGN	XM_017029724.3	c.238+75A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BGN	ENST00000331595.9	c.238+75A>G		intron_variant		1	NM_001711.6	P1
BGN	ENST00000431891.1	c.238+75A>G		intron_variant		5
BGN	ENST00000472615.5	n.382+75A>G		intron_variant, non_coding_transcript_variant		5
BGN	ENST00000480756.1	n.329+126A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.872 AC: 96724 AN: 110882 Hom.: 29975 Cov.: 23 AF XY: 0.878 AC XY: 29039 AN XY: 33088

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

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.969

Gnomad4 ASJ exome AF: 0.912

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.953

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.941

Gnomad4 OTH exome AF: 0.925

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

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.878

Alfa AF: 0.846 Hom.: 3502

Bravo AF: 0.864

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

X-linked spondyloepimetaphyseal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Meester-Loeys syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.96
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2980053; hg19: chrX-152770402;