rs7838961

Variant names:

• chr8-22181439-G-A
• rs7838961
• NM_006129.5:c.1077+956G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22181439-G-A
• chr8-22181439-G-C

Variant summary

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

The NM_006129.5(BMP1):​c.1077+956G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,018 control chromosomes in the GnomAD database, including 24,050 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 0.56 (24050 hom., cov: 32)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 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.1077+956G>A		intron	N/A	NP_006120.1	P13497-1
	BMP1	NM_001199.4	MANE Plus Clinical	c.1077+956G>A		intron	N/A	NP_001190.1	P13497-2
	BMP1	NR_033403.2		n.1148+956G>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.1077+956G>A		intron	N/A	ENSP00000305714.5	P13497-1
	BMP1	ENST00000306349.13	TSL:1 MANE Plus Clinical	c.1077+956G>A		intron	N/A	ENSP00000306121.8	P13497-2
	BMP1	ENST00000471755.5	TSL:1	n.1077+956G>A		intron	N/A	ENSP00000428665.1	P13497-4

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84572 AN: 151900 Hom.: 24004 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.557 AC: 84666 AN: 152018 Hom.: 24050 Cov.: 32 AF XY: 0.562 AC XY: 41776 AN XY: 74286

African (AFR) AF: 0.656 AC: 27220 AN: 41472

American (AMR) AF: 0.585 AC: 8932 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1789 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5162

South Asian (SAS) AF: 0.529 AC: 2547 AN: 4818

European-Finnish (FIN) AF: 0.594 AC: 6279 AN: 10568

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32532 AN: 67934

Other (OTH) AF: 0.569 AC: 1200 AN: 2110

Alfa AF: 0.508 Hom.: 63437

Bravo AF: 0.561

Asia WGS AF: 0.632 AC: 2196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.98
DANN	Benign	0.48
PhyloP100		-1.0
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: rs7838961; hg19: chr8-22038952;