rs1362079805

Variant names:

• chr8-22165454-C-A
• rs1362079805
• NM_006129.5:c.49C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22165454-C-A
• chr8-22165454-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006129.5(BMP1):​c.49C>A​(p.Pro17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BMP1 NM_006129.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13999629).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	NM_006129.5	MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 20	NP_006120.1	P13497-1
	BMP1	NM_001199.4	MANE Plus Clinical	c.49C>A	p.Pro17Thr	missense	Exon 1 of 16	NP_001190.1	P13497-2
	BMP1	NR_033403.2		n.83C>A		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	ENST00000306385.10	TSL:1 MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 20	ENSP00000305714.5	P13497-1
	BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.49C>A	p.Pro17Thr	missense	Exon 1 of 16	ENSP00000306121.8	P13497-2
	BMP1	ENST00000471755.5	TSL:1	n.49C>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000428665.1	P13497-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.29
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.039
Sift	Benign	0.21	T
Sift4G	Benign	0.15	T
Polyphen		0.036	B
Vest4		0.16
MutPred		0.24		Loss of disorder (P = 0.0369)
MVP		0.65
MPC		0.44
ClinPred		0.058	T
GERP RS		-2.0
PromoterAI		-0.033	Neutral
Varity_R		0.070
gMVP		0.31
Mutation Taster		=94/6	polymorphism

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: rs1362079805; hg19: chr8-22022967;