X-153504606-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001711.6(BGN):c.-11-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,151,918 control chromosomes in the GnomAD database, including 12 homozygotes. There are 294 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (2 hom., 25 hem., cov: 25)
  • Exomes 𝑓: 0.00091 (10 hom. 269 hem.)
• Consequence: BGN NM_001711.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-153504606-C-G is Benign according to our data. Variant chrX-153504606-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000806 (91/112845) while in subpopulation EAS AF= 0.0235 (83/3532). AF 95% confidence interval is 0.0194. There are 2 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BGN	NM_001711.6	c.-11-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000331595.9
BGN	XM_017029724.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BGN	ENST00000331595.9	c.-11-15C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001711.6	P1
BGN	ENST00000431891.1	c.-11-15C>G		splice_polypyrimidine_tract_variant, intron_variant		5
BGN	ENST00000472615.5	n.134-15C>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
BGN	ENST00000480756.1	n.132-15C>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000807 AC: 91 AN: 112792 Hom.: 2 Cov.: 25 AF XY: 0.000715 AC XY: 25 AN XY: 34948

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00233 AC: 377 AN: 161854 Hom.: 4 AF XY: 0.00224 AC XY: 115 AN XY: 51344

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000397

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0272

Gnomad SAS exome AF: 0.000537

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.000906 AC: 941 AN: 1039073 Hom.: 10 Cov.: 26 AF XY: 0.000827 AC XY: 269 AN XY: 325357

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000596

Gnomad4 ASJ exome AF: 0.0000558

Gnomad4 EAS exome AF: 0.0288

Gnomad4 SAS exome AF: 0.000493

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000628

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.000806 AC: 91 AN: 112845 Hom.: 2 Cov.: 25 AF XY: 0.000714 AC XY: 25 AN XY: 35011

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000185

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.00109

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000563

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.00143

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

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs181456114; hg19: chrX-152770064;