rs1042103

chrX-153508573-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001711.6(BGN):c.*128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 833,191 control chromosomes in the GnomAD database, including 38,897 homozygotes. There are 79,348 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (3641 hom., 8625 hem., cov: 23)
  • Exomes 𝑓: 0.36 (35256 hom. 70723 hem.)
• Consequence: BGN NM_001711.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.56

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=-0.92).
• BP6: Variant X-153508573-G-A is Benign according to our data. Variant chrX-153508573-G-A is described in ClinVar as [Benign]. Clinvar id is 1263317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BGN	NM_001711.6	c.*128G>A		3_prime_UTR_variant	8/8	ENST00000331595.9
BGN	XM_017029724.3	c.*128G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BGN	ENST00000331595.9	c.*128G>A		3_prime_UTR_variant	8/8	1	NM_001711.6	P1
BGN	ENST00000472615.5	n.1252G>A		non_coding_transcript_exon_variant	8/8	5
BGN	ENST00000480756.1	n.1305G>A		non_coding_transcript_exon_variant	8/8	5
BGN	ENST00000492658.1	n.295-107G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 29592 AN: 111109 Hom.: 3642 Cov.: 23 AF XY: 0.258 AC XY: 8624 AN XY: 33385

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.357 AC: 257908 AN: 722029 Hom.: 35256 Cov.: 11 AF XY: 0.374 AC XY: 70723 AN XY: 189055

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.0797

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.266 AC: 29585 AN: 111162 Hom.: 3641 Cov.: 23 AF XY: 0.258 AC XY: 8625 AN XY: 33448

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.230

Alfa AF: 0.352 Hom.: 9667

Bravo AF: 0.240

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.11
Dann	Benign	0.44

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: rs1042103; hg19: chrX-152774031;