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GeneBe

X-153504657-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_001711.6(BGN):c.26C>T(p.Ser9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,094,359 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S9S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.000010 ( 0 hom. 2 hem. )

Consequence

BGN
NM_001711.6 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266
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 -3 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.114940375).
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000101 (11/1094359) while in subpopulation AMR AF= 0.000143 (5/35000). AF 95% confidence interval is 0.0000554. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BGNNM_001711.6 linkuse as main transcriptc.26C>T p.Ser9Phe missense_variant 2/8 ENST00000331595.9
BGNXM_017029724.3 linkuse as main transcriptc.26C>T p.Ser9Phe missense_variant 1/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BGNENST00000331595.9 linkuse as main transcriptc.26C>T p.Ser9Phe missense_variant 2/81 NM_001711.6 P1
BGNENST00000431891.1 linkuse as main transcriptc.26C>T p.Ser9Phe missense_variant 2/55
BGNENST00000472615.5 linkuse as main transcriptn.170C>T non_coding_transcript_exon_variant 2/85
BGNENST00000480756.1 linkuse as main transcriptn.168C>T non_coding_transcript_exon_variant 2/85

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.0000276
AC:
5
AN:
181013
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
65773
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000148
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:
0.00
GnomAD4 exome
AF:
0.0000101
AC:
11
AN:
1094359
Hom.:
0
Cov.:
30
AF XY:
0.00000555
AC XY:
2
AN XY:
360313
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000143
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:
0.00000476
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
Cov.:
24
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 testingInvitaeAug 18, 2021Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This sequence change replaces serine with phenylalanine at codon 9 of the BGN protein (p.Ser9Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs782144541, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with BGN-related conditions. 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
Benign
0.083
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
7.9
Dann
Benign
0.96
DEOGEN2
Benign
0.099
T;T
FATHMM_MKL
Benign
0.075
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.058
Sift
Benign
0.23
T;T
Sift4G
Benign
0.70
T;T
Polyphen
0.12
B;.
Vest4
0.13
MutPred
0.47
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.42
MPC
0.34
ClinPred
0.031
T
GERP RS
2.7
Varity_R
0.068
gMVP
0.49

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

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

Other links and lift over

dbSNP: rs782144541; hg19: chrX-152770115; API