Variant rs3733549 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001201.5(BMP3):c.575G>A(p.Arg192Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0806 in 1,613,884 control chromosomes in the GnomAD database, including 6,786 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 587 hom., cov: 33)

Exomes 𝑓: 0.081 ( 6199 hom. )

Consequence

BMP3
NM_001201.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

BMP3 (HGNC:1070): (bone morphogenetic protein 3) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein suppresses osteoblast differentiation, and negatively regulates bone density, by modulating TGF-beta receptor availability to other ligands. [provided by RefSeq, Jul 2016]

BMP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019924939).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP3	NM_001201.5 linkuse as main transcript	c.575G>A	p.Arg192Gln	missense_variant	2/3	ENST00000282701.4	NP_001192.4
BMP3	XM_006714291.4 linkuse as main transcript	c.575G>A	p.Arg192Gln	missense_variant	2/3		XP_006714354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP3	ENST00000282701.4 linkuse as main transcript	c.575G>A	p.Arg192Gln	missense_variant	2/3	1	NM_001201.5	ENSP00000282701	P1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12062

AN:

152086

Hom.:

589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0706

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0593

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0864

GnomAD3 exomes

AF:

0.101

AC:

25460

AN:

250960

Hom.:

1767

AF XY:

0.107

AC XY:

14507

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.0676

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.0606

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.0525

Gnomad NFE exome

AF:

0.0697

Gnomad OTH exome

AF:

0.0829

GnomAD4 exome

AF:

0.0807

AC:

117951

AN:

1461680

Hom.:

6199

Cov.:

AF XY:

0.0851

AC XY:

61915

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.0589

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.0550

Gnomad4 NFE exome

AF:

0.0668

Gnomad4 OTH exome

AF:

0.0828

GnomAD4 genome

AF:

0.0792

AC:

12062

AN:

152204

Hom.:

587

Cov.:

AF XY:

0.0820

AC XY:

6104

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0706

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0593

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0676

Gnomad4 OTH

AF:

0.0865

Alfa

AF:

0.0662

Hom.:

230

Bravo

AF:

0.0792

TwinsUK

AF:

0.0685

AC:

254

ALSPAC

AF:

0.0628

AC:

242

ESP6500AA

AF:

0.0690

AC:

304

ESP6500EA

AF:

0.0688

AC:

592

ExAC

AF:

0.104

AC:

12678

Asia WGS

AF:

0.208

AC:

726

AN:

3478

EpiCase

AF:

0.0701

EpiControl

AF:

0.0671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.0

DANN

Benign

0.95

DEOGEN2

Benign

0.27

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.0093

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.2

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.10

Polyphen

0.039

Vest4

0.021

MPC

0.13

ClinPred

0.017

GERP RS

3.1

Varity_R

0.028

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over