X-153504652-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001711.6(BGN):c.21C>T(p.Leu7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,206,566 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 25)
  • Exomes 𝑓: 0.000012 (0 hom. 3 hem.)
• Consequence: BGN NM_001711.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.61

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant X-153504652-C-T is Benign according to our data. Variant chrX-153504652-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1930858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000266 (3/112835) while in subpopulation AMR AF= 0.000185 (2/10799). AF 95% confidence interval is 0.0000325. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BGN	NM_001711.6	c.21C>T	p.Leu7=	synonymous_variant	2/8	ENST00000331595.9
BGN	XM_017029724.3	c.21C>T	p.Leu7=	synonymous_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BGN	ENST00000331595.9	c.21C>T	p.Leu7=	synonymous_variant	2/8	1	NM_001711.6	P1
BGN	ENST00000431891.1	c.21C>T	p.Leu7=	synonymous_variant	2/5	5
BGN	ENST00000472615.5	n.165C>T		non_coding_transcript_exon_variant	2/8	5
BGN	ENST00000480756.1	n.163C>T		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 3 AN: 112835 Hom.: 0 Cov.: 25 AF XY: 0.0000286 AC XY: 1 AN XY: 34981

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000444 AC: 8 AN: 180299 Hom.: 0 AF XY: 0.0000307 AC XY: 2 AN XY: 65141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000222

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.0000119 AC: 13 AN: 1093731 Hom.: 0 Cov.: 30 AF XY: 0.00000834 AC XY: 3 AN XY: 359785

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000171

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000596

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome AF: 0.0000266 AC: 3 AN: 112835 Hom.: 0 Cov.: 25 AF XY: 0.0000286 AC XY: 1 AN XY: 34981

Gnomad4 AFR AF: 0.0000322

Gnomad4 AMR AF: 0.000185

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 04, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.41
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199928539; hg19: chrX-152770110;