rs1171944003

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_006129.5(BMP1):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000803 in 1,494,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

BMP1
NM_006129.5 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.23

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 8 pathogenic variants. Next in-frame start position is after 155 codons. Genomic position: 22176562. Lost 0.156 part of the original CDS.

PP5

Variant 8-22165406-A-G is Pathogenic according to our data. Variant chr8-22165406-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 2987540.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1A>G	p.Met1?	start_lost	Exon 1 of 20	NP_006120.1	P13497-1
BMP1	NM_001199.4	MANE Plus Clinical	c.1A>G	p.Met1?	start_lost	Exon 1 of 16	NP_001190.1	P13497-2
BMP1	NR_033403.2		n.35A>G		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.1A>G	p.Met1?	start_lost	Exon 1 of 20	ENSP00000305714.5	P13497-1
BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.1A>G	p.Met1?	start_lost	Exon 1 of 16	ENSP00000306121.8	P13497-2
BMP1	ENST00000471755.5	TSL:1	n.1A>G		non_coding_transcript_exon	Exon 1 of 16	ENSP00000428665.1	P13497-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

104336

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000819

AC:

AN:

1342674

Hom.:

Cov.:

AF XY:

0.00000603

AC XY:

AN XY:

663438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26966

American (AMR)

AF:

0.00

AC:

AN:

22390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22030

East Asian (EAS)

AF:

0.00

AC:

AN:

30930

South Asian (SAS)

AF:

0.00

AC:

AN:

71276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.0000104

AC:

AN:

1060910

Other (OTH)

AF:

0.00

AC:

AN:

55230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.044

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.99

MetaSVM

Benign

-0.40

PhyloP100

1.2

PROVEAN

Benign

-1.1

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.86

MutPred

1.0

Loss of disorder (P = 0.1132)

MVP

0.92

ClinPred

0.84

GERP RS

3.3

PromoterAI

-0.13

Neutral

(source)

Varity_R

0.93

gMVP

0.59

Mutation Taster

=19/181

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over