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GeneBe

X-153504683-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001711.6(BGN):c.52C>T(p.Pro18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,210,522 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 24)
Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

BGN
NM_001711.6 missense

Scores

4
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000886 (10/112824) while in subpopulation AMR AF= 0.000928 (10/10780). AF 95% confidence interval is 0.000502. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BGNNM_001711.6 linkuse as main transcriptc.52C>T p.Pro18Ser missense_variant 2/8 ENST00000331595.9
BGNXM_017029724.3 linkuse as main transcriptc.52C>T p.Pro18Ser missense_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BGNENST00000331595.9 linkuse as main transcriptc.52C>T p.Pro18Ser missense_variant 2/81 NM_001711.6 P1
BGNENST00000431891.1 linkuse as main transcriptc.52C>T p.Pro18Ser missense_variant 2/55
BGNENST00000472615.5 linkuse as main transcriptn.196C>T non_coding_transcript_exon_variant 2/85
BGNENST00000480756.1 linkuse as main transcriptn.194C>T non_coding_transcript_exon_variant 2/85

Frequencies

GnomAD3 genomes
AF:
0.0000886
AC:
10
AN:
112824
Hom.:
0
Cov.:
24
AF XY:
0.0000858
AC XY:
3
AN XY:
34976
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000928
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:
0.0000328
AC:
6
AN:
183014
Hom.:
0
AF XY:
0.0000444
AC XY:
3
AN XY:
67542
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000219
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
6
AN:
1097698
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
3
AN XY:
363150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000170
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000886
AC:
10
AN:
112824
Hom.:
0
Cov.:
24
AF XY:
0.0000858
AC XY:
3
AN XY:
34976
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000928
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
Bravo
AF:
0.0000718

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJul 25, 2023This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 18 of the BGN protein (p.Pro18Ser). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BGN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1925100). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.28
Cadd
Pathogenic
26
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D;T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Uncertain
0.33
D
MutationAssessor
Pathogenic
3.1
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-5.4
D;D
REVEL
Uncertain
0.60
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.56
MutPred
0.64
Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP
0.87
MPC
1.0
ClinPred
0.85
D
GERP RS
4.7
Varity_R
0.84
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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.

Other links and lift over

dbSNP: rs1305457220; hg19: chrX-152770141; COSMIC: COSV59036806; COSMIC: COSV59036806; API