X-153506075-C-T

Position:

chrX-153506075-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001711.6(BGN):c.564C>T(p.Ile188Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,207,610 control chromosomes in the GnomAD database, including 286 homozygotes. There are 6,479 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 99 hom., 1075 hem., cov: 23)

Exomes 𝑓: 0.015 ( 187 hom. 5404 hem. )

Consequence

BGN
NM_001711.6 splice_region, synonymous

Scores

Splicing: ADA: 0.001369

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.15

Variant links:

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 links:

BGN (HGNC:):

BGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant X-153506075-C-T is Benign according to our data. Variant chrX-153506075-C-T is described in ClinVar as [Benign]. Clinvar id is 1167739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153506075-C-T is described in Lovd as [Benign]. Variant chrX-153506075-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BGN	NM_001711.6 linkuse as main transcript	c.564C>T	p.Ile188Ile	splice_region_variant, synonymous_variant	4/8	ENST00000331595.9	NP_001702.1	P21810B4DNL4
BGN	XM_017029724.3 linkuse as main transcript	c.564C>T	p.Ile188Ile	splice_region_variant, synonymous_variant	3/7		XP_016885213.1	P21810

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BGN	ENST00000331595.9 linkuse as main transcript	c.564C>T	p.Ile188Ile	splice_region_variant, synonymous_variant	4/8	1	NM_001711.6	ENSP00000327336.4		P21810

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

3809

AN:

112234

Hom.:

Cov.:

AF XY:

0.0311

AC XY:

1070

AN XY:

34400

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0557

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00583

Gnomad MID

AF:

0.0125

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0235

AC:

4272

AN:

181513

Hom.:

101

AF XY:

0.0200

AC XY:

1328

AN XY:

66291

show subpopulations

Gnomad AFR exome

AF:

0.0854

Gnomad AMR exome

AF:

0.00647

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.0896

Gnomad SAS exome

AF:

0.00743

Gnomad FIN exome

AF:

0.00659

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0155

AC:

16939

AN:

1095322

Hom.:

187

Cov.:

AF XY:

0.0150

AC XY:

5404

AN XY:

360902

show subpopulations

Gnomad4 AFR exome

AF:

0.0848

Gnomad4 AMR exome

AF:

0.00745

Gnomad4 ASJ exome

AF:

0.0555

Gnomad4 EAS exome

AF:

0.0756

Gnomad4 SAS exome

AF:

0.00880

Gnomad4 FIN exome

AF:

0.00755

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0340

AC:

3818

AN:

112288

Hom.:

Cov.:

AF XY:

0.0312

AC XY:

1075

AN XY:

34464

show subpopulations

Gnomad4 AFR

AF:

0.0790

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0557

Gnomad4 EAS

AF:

0.0777

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00583

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0194

Hom.:

883

Bravo

AF:

0.0377

EpiCase

AF:

0.0123

EpiControl

AF:

0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 16, 2018	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 21, 2023	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.22

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over