rs7812993

Variant names:

• chr8-22168131-G-A
• rs7812993
• NM_006129.5:c.148+2578G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22168131-G-A
• chr8-22168131-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.148+2578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,946 control chromosomes in the GnomAD database, including 42,139 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 0.74 (42139 hom., cov: 30)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP1	NM_006129.5	c.148+2578G>A		intron_variant	Intron 1 of 19	ENST00000306385.10	NP_006120.1
BMP1	NM_001199.4	c.148+2578G>A		intron_variant	Intron 1 of 15	ENST00000306349.13	NP_001190.1
BMP1	NR_033403.2	n.182+2578G>A		intron_variant	Intron 1 of 19
BMP1	NR_033404.2	n.182+2578G>A		intron_variant	Intron 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.148+2578G>A		intron_variant	Intron 1 of 19	1	NM_006129.5	ENSP00000305714.5
BMP1	ENST00000306349.13	c.148+2578G>A		intron_variant	Intron 1 of 15	1	NM_001199.4	ENSP00000306121.8

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112927 AN: 151828 Hom.: 42105 Cov.: 30

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.744 AC: 113010 AN: 151946 Hom.: 42139 Cov.: 30 AF XY: 0.740 AC XY: 54950 AN XY: 74252

African (AFR) AF: 0.712 AC: 29478 AN: 41416

American (AMR) AF: 0.792 AC: 12105 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2706 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3175 AN: 5132

South Asian (SAS) AF: 0.601 AC: 2889 AN: 4808

European-Finnish (FIN) AF: 0.747 AC: 7887 AN: 10554

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52230 AN: 67968

Other (OTH) AF: 0.757 AC: 1597 AN: 2110

Alfa AF: 0.764 Hom.: 181952

Bravo AF: 0.752

Asia WGS AF: 0.607 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.12
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: rs7812993; hg19: chr8-22025644;