dbSNP rs786205217: BMP1:c.*241T>C (chr8-22201444-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5BP4

The NM_001199.4(BMP1):c.*241T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000852 in 1,408,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000088 ( 0 hom. )

Consequence

BMP1
NM_001199.4 3_prime_UTR

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.63

Publications

3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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: Uncertain_significance. The variant received 0 ACMG points.

PP5

Variant 8-22201444-T-C is Pathogenic according to our data. Variant chr8-22201444-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 190231.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BMP1	NM_001199.4	MANE Plus Clinical	c.*241T>C	3_prime_UTR	Exon 16 of 16	NP_001190.1
BMP1	NM_006129.5	MANE Select	c.2108-359T>C	intron	N/A	NP_006120.1
BMP1	NR_033404.2		n.2505T>C	non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.*241T>C	3_prime_UTR	Exon 16 of 16	ENSP00000306121.8
BMP1	ENST00000306385.10	TSL:1 MANE Select	c.2108-359T>C	intron	N/A	ENSP00000305714.5
BMP1	ENST00000518913.5	TSL:1	n.*1901T>C	non_coding_transcript_exon	Exon 16 of 16	ENSP00000427950.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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

GnomAD4 exome

AF:

0.00000876

AC:

AN:

1256420

Hom.:

Cov.:

AF XY:

0.00000658

AC XY:

AN XY:

607904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27276

American (AMR)

AF:

0.00

AC:

AN:

15978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18164

East Asian (EAS)

AF:

0.00

AC:

AN:

31432

South Asian (SAS)

AF:

0.00

AC:

AN:

59550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3478

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1019478

Other (OTH)

AF:

0.00

AC:

AN:

51882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

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 as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis imperfecta type 13 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

4.6

Mutation Taster

=34/66

disease causing (ClinVar)

(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