NM_006129.5:c.2233+165G>A

Variant names:

• chr8-22202093-G-A
• rs13257482
• NM_006129.5:c.2233+165G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006129.5(BMP1):​c.2233+165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,152 control chromosomes in the GnomAD database, including 16,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.39 (16710 hom., cov: 33)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.10
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-22202093-G-A is Benign according to our data. Variant chr8-22202093-G-A is described in ClinVar as Benign. ClinVar VariationId is 680516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	NM_006129.5	MANE Select	c.2233+165G>A		intron	N/A	NP_006120.1	P13497-1
	BMP1	NR_033403.2		n.2304+165G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	ENST00000306385.10	TSL:1 MANE Select	c.2233+165G>A		intron	N/A	ENSP00000305714.5	P13497-1
	BMP1	ENST00000520626.6	TSL:1	n.*2765+165G>A		intron	N/A	ENSP00000430015.2	E5RH22
	BMP1	ENST00000520970.5	TSL:1	n.*725+165G>A		intron	N/A	ENSP00000428332.1	P13497-2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59561 AN: 152034 Hom.: 16657 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.392 AC: 59671 AN: 152152 Hom.: 16710 Cov.: 33 AF XY: 0.392 AC XY: 29122 AN XY: 74372

African (AFR) AF: 0.800 AC: 33220 AN: 41506

American (AMR) AF: 0.302 AC: 4623 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5174

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3223 AN: 10600

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14814 AN: 67980

Other (OTH) AF: 0.349 AC: 737 AN: 2110

Alfa AF: 0.279 Hom.: 15806

Bravo AF: 0.410

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.057
DANN	Benign	0.36
PhyloP100		-2.1
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: rs13257482; hg19: chr8-22059606; COSMIC: COSV107385285; COSMIC: COSV107385285;