8-22165142-CGGAGGGAG-CGGAGGGAGGGAG

Variant names:

• chr8-22165149-A-AGGGA
• ENST00000354870.5:c.-247_-244dupGGAG

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 was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMP1 ENST00000397814.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	NM_006129.5	MANE Select	c.-257_-256insGGGA		upstream_gene	N/A	NP_006120.1	P13497-1
	BMP1	NM_001199.4	MANE Plus Clinical	c.-257_-256insGGGA		upstream_gene	N/A	NP_001190.1	P13497-2
	BMP1	NR_033403.2		n.-223_-222insGGGA		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.-260_-257dupGGGA		upstream_gene	N/A	ENSP00000305714.5	P13497-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-22022662;