rs11775186

Variant names:

• chr8-22200609-T-G
• rs11775186
• NM_006129.5:c.2108-1194T>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.2108-1194T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,124 control chromosomes in the GnomAD database, including 637 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 0.089 (637 hom., cov: 32)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 8 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP1	NM_006129.5	c.2108-1194T>G		intron_variant	Intron 15 of 19	ENST00000306385.10	NP_006120.1
BMP1	NM_001199.4	c.2108-509T>G		intron_variant	Intron 15 of 15	ENST00000306349.13	NP_001190.1
BMP1	NR_033403.2	n.2179-1194T>G		intron_variant	Intron 15 of 19
BMP1	NR_033404.2	n.2179-509T>G		intron_variant	Intron 15 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.2108-1194T>G		intron_variant	Intron 15 of 19	1	NM_006129.5	ENSP00000305714.5
BMP1	ENST00000306349.13	c.2108-509T>G		intron_variant	Intron 15 of 15	1	NM_001199.4	ENSP00000306121.8

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13540 AN: 152006 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0890 AC: 13542 AN: 152124 Hom.: 637 Cov.: 32 AF XY: 0.0883 AC XY: 6564 AN XY: 74368

African (AFR) AF: 0.0816 AC: 3386 AN: 41508

American (AMR) AF: 0.0818 AC: 1251 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.0915 AC: 474 AN: 5178

South Asian (SAS) AF: 0.102 AC: 494 AN: 4826

European-Finnish (FIN) AF: 0.0805 AC: 852 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6540 AN: 67948

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0895 Hom.: 1064

Bravo AF: 0.0875

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.053
DANN	Benign	0.70
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11775186; hg19: chr8-22058122;