Genetic Variant BMP1:c.-247_-244dupGGAG (chr8-22165142-C-CGGAG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000397814.7(BMP1):c.-247_-244dupGGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 346,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

BMP1
ENST00000397814.7 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397814.7. 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.-264_-263insGGAG	upstream_gene	N/A	NP_006120.1	P13497-1
BMP1	NM_001199.4	MANE Plus Clinical	c.-264_-263insGGAG	upstream_gene	N/A	NP_001190.1	P13497-2
BMP1	NR_033403.2		n.-230_-229insGGAG	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP1	ENST00000354870.5	TSL:5	c.-247_-244dupGGAG	5_prime_UTR	Exon 1 of 21	ENSP00000346941.5	Q3MIM8
BMP1	ENST00000397814.7	TSL:4	c.-247_-244dupGGAG	5_prime_UTR	Exon 1 of 5	ENSP00000380915.4	B7ZKR5
BMP1	ENST00000306385.10	TSL:1 MANE Select	c.-264_-263insGGAG	upstream_gene	N/A	ENSP00000305714.5	P13497-1

Frequencies

GnomAD3 genomes

AF:

0.0000165

AC:

AN:

121570

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:

0.0000357

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

224652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

115686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5388

American (AMR)

AF:

0.00

AC:

AN:

5026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7554

East Asian (EAS)

AF:

0.000127

AC:

AN:

15758

South Asian (SAS)

AF:

0.00

AC:

AN:

13642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1096

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

143668

Other (OTH)

AF:

0.00

AC:

AN:

14374

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

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:

0.0000165

AC:

AN:

121570

Hom.:

Cov.:

AF XY:

0.0000341

AC XY:

AN XY:

58670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33352

American (AMR)

AF:

0.00

AC:

AN:

12716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2982

East Asian (EAS)

AF:

0.00

AC:

AN:

3236

South Asian (SAS)

AF:

0.00

AC:

AN:

3392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.0000357

AC:

AN:

56070

Other (OTH)

AF:

0.00

AC:

AN:

1680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-22165142-CGGAGGGAG-CGGAGGGAGGGAG

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