rs750344454

Variant names:

• chr8-22165142-CGGAGGGAG-C
• rs750344454
• ENST00000354870.5:c.-251_-244delGGAGGGAG

Your query was ambiguous. Multiple possible variants found:

• chr8-22165142-CGGAGGGAG-C
• chr8-22165142-CGGAGGGAG-CGGAG
• chr8-22165142-CGGAGGGAG-CGGAGGGAGGGAG

Variant summary

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

The ENST00000397814.7(BMP1):​c.-251_-244delGGAGGGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 345,962 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 0.000033 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: BMP1 ENST00000397814.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• 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 0 ACMG points.

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.-263_-256delGGAGGGAG		upstream_gene	N/A	NP_006120.1	P13497-1
	BMP1	NM_001199.4	MANE Plus Clinical	c.-263_-256delGGAGGGAG		upstream_gene	N/A	NP_001190.1	P13497-2
	BMP1	NR_033403.2		n.-229_-222delGGAGGGAG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	ENST00000354870.5	TSL:5	c.-251_-244delGGAGGGAG		5_prime_UTR	Exon 1 of 21	ENSP00000346941.5	Q3MIM8
	BMP1	ENST00000397814.7	TSL:4	c.-251_-244delGGAGGGAG		5_prime_UTR	Exon 1 of 5	ENSP00000380915.4	B7ZKR5
	BMP1	ENST00000306385.10	TSL:1 MANE Select	c.-263_-256delGGAGGGAG		upstream_gene	N/A	ENSP00000305714.5	P13497-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 4 AN: 121568 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000600

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: 0.0000980 AC: 22 AN: 224394 Hom.: 0 AF XY: 0.0000952 AC XY: 11 AN XY: 115570

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5386

American (AMR) AF: 0.000199 AC: 1 AN: 5016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7550

East Asian (EAS) AF: 0.00 AC: 0 AN: 15758

South Asian (SAS) AF: 0.0000734 AC: 1 AN: 13632

European-Finnish (FIN) AF: 0.000166 AC: 3 AN: 18114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1096

European-Non Finnish (NFE) AF: 0.000105 AC: 15 AN: 143486

Other (OTH) AF: 0.000139 AC: 2 AN: 14356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000329 AC: 4 AN: 121568 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 58670

African (AFR) AF: 0.0000600 AC: 2 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 12714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2982

East Asian (EAS) AF: 0.00 AC: 0 AN: 3236

South Asian (SAS) AF: 0.00 AC: 0 AN: 3392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000357 AC: 2 AN: 56070

Other (OTH) AF: 0.00 AC: 0 AN: 1680

Alfa AF: 0.00 Hom.: 65

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs750344454; hg19: chr8-22022655;