Genetic Variant BMP1:c.-15C>G (chr8-22165391-C-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006129.5(BMP1):c.-15C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,446,040 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

BMP1
NM_006129.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.397

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 8-22165391-C-G is Benign according to our data. Variant chr8-22165391-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 362575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00798 (1215/152268) while in subpopulation NFE AF = 0.0135 (919/67996). AF 95% confidence interval is 0.0128. There are 9 homozygotes in GnomAd4. There are 536 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR,AD gene

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	Effect	Exon Rank	Protein	UniProt
BMP1	NM_006129.5	MANE Select	c.-15C>G	5_prime_UTR	Exon 1 of 20	NP_006120.1	P13497-1
BMP1	NM_001199.4	MANE Plus Clinical	c.-15C>G	5_prime_UTR	Exon 1 of 16	NP_001190.1	P13497-2
BMP1	NR_033403.2		n.20C>G	non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP1	ENST00000306385.10	TSL:1 MANE Select	c.-15C>G	5_prime_UTR	Exon 1 of 20	ENSP00000305714.5	P13497-1
BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.-15C>G	5_prime_UTR	Exon 1 of 16	ENSP00000306121.8	P13497-2
BMP1	ENST00000518656.5	TSL:1	n.-15C>G	non_coding_transcript_exon	Exon 1 of 7	ENSP00000430977.1	B7ZKR5

Frequencies

GnomAD3 genomes

AF:

0.00800

AC:

1217

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00730

AC:

392

AN:

53690

AF XY:

0.00739

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00534

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00468

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00613

GnomAD4 exome

AF:

0.0124

AC:

16024

AN:

1293772

Hom.:

130

Cov.:

AF XY:

0.0123

AC XY:

7808

AN XY:

635606

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

25464

American (AMR)

AF:

0.00645

AC:

102

AN:

15810

Ashkenazi Jewish (ASJ)

AF:

0.00474

AC:

AN:

19194

East Asian (EAS)

AF:

0.0000687

AC:

AN:

29104

South Asian (SAS)

AF:

0.00425

AC:

270

AN:

63460

European-Finnish (FIN)

AF:

0.00445

AC:

204

AN:

45820

Middle Eastern (MID)

AF:

0.00328

AC:

AN:

4580

European-Non Finnish (NFE)

AF:

0.0142

AC:

14692

AN:

1037224

Other (OTH)

AF:

0.0113

AC:

601

AN:

53116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

866

1732

2597

3463

4329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.00798

AC:

1215

AN:

152268

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41572

American (AMR)

AF:

0.00654

AC:

100

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00373

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0135

AC:

919

AN:

67996

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00932

Hom.:

Bravo

AF:

0.00785

Asia WGS

AF:

0.000870

AC:

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Interstitial lung disease 2 (1)

not provided (1)

not specified (1)

Osteogenesis imperfecta type 13 (1)

Osteogenesis Imperfecta, Recessive (1)

Pulmonary Surfactant Metabolism Dysfunction, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.40

PromoterAI

-0.081

Neutral

(source)

Mutation Taster

=300/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over