8-22191277-T-G

Variant names:

• chr8-22191277-T-G
• rs12114940
• NM_006129.5:c.1078-772T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006129.5(BMP1):​c.1078-772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,942 control chromosomes in the GnomAD database, including 12,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12278 hom., cov: 32)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 15 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: 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

ENSG00000285881 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	NM_006129.5	MANE Select	c.1078-772T>G		intron	N/A	NP_006120.1
	BMP1	NM_001199.4	MANE Plus Clinical	c.1078-772T>G		intron	N/A	NP_001190.1
	BMP1	NR_033403.2		n.1149-772T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	ENST00000306385.10	TSL:1 MANE Select	c.1078-772T>G		intron	N/A	ENSP00000305714.5
	BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.1078-772T>G		intron	N/A	ENSP00000306121.8
	BMP1	ENST00000471755.5	TSL:1	n.1078-772T>G		intron	N/A	ENSP00000428665.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59254 AN: 151824 Hom.: 12272 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59280 AN: 151942 Hom.: 12278 Cov.: 32 AF XY: 0.390 AC XY: 28990 AN XY: 74254

African (AFR) AF: 0.259 AC: 10726 AN: 41432

American (AMR) AF: 0.424 AC: 6474 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3311 AN: 5158

South Asian (SAS) AF: 0.475 AC: 2287 AN: 4816

European-Finnish (FIN) AF: 0.420 AC: 4434 AN: 10558

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28995 AN: 67932

Other (OTH) AF: 0.424 AC: 893 AN: 2106

Alfa AF: 0.421 Hom.: 13356

Bravo AF: 0.385

Asia WGS AF: 0.535 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12114940; hg19: chr8-22048790;