Genetic Variant BMP1:p.Pro17Ser (chr8-22165454-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006129.5(BMP1):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. P17P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMP1
NM_006129.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.293

Publications

1 publications found

Variant links:

Genes affected

BMP1 (HGNC:1067): (bone morphogenetic protein 1) This gene encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, this gene encodes a protein that is not closely related to other known growth factors. This gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region. [provided by RefSeq, Aug 2008]

BMP1 Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 13
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
high bone mass osteogenesis imperfecta
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BMP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110814184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006129.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMP1	NM_006129.5	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 20	NP_006120.1	P13497-1
BMP1	NM_001199.4	MANE Plus Clinical	c.49C>T	p.Pro17Ser	missense	Exon 1 of 16	NP_001190.1	P13497-2
BMP1	NR_033403.2		n.83C>T		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMP1	ENST00000306385.10	TSL:1 MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 20	ENSP00000305714.5	P13497-1
BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.49C>T	p.Pro17Ser	missense	Exon 1 of 16	ENSP00000306121.8	P13497-2
BMP1	ENST00000471755.5	TSL:1	n.49C>T		non_coding_transcript_exon	Exon 1 of 16	ENSP00000428665.1	P13497-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710410

African (AFR)

AF:

0.00

AC:

AN:

29650

American (AMR)

AF:

0.00

AC:

AN:

40490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25010

East Asian (EAS)

AF:

0.00

AC:

AN:

34996

South Asian (SAS)

AF:

0.00

AC:

AN:

82836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099218

Other (OTH)

AF:

0.00

AC:

AN:

58794

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis imperfecta (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.089

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PhyloP100

-0.29

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.91

REVEL

Benign

0.033

Sift

Benign

0.55

Sift4G

Benign

0.43

Polyphen

0.0010

Vest4

0.15

MutPred

0.20

Loss of loop (P = 0.0374)

MVP

0.53

MPC

0.40

ClinPred

0.050

GERP RS

-2.0

PromoterAI

0.052

Neutral

(source)

Varity_R

0.044

gMVP

0.30

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over