rs3857979

Variant names:

• chr8-22197835-C-T
• rs3857979
• NM_006129.5:c.2107+415C>T

Variant summary

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

The NM_006129.5(BMP1):​c.2107+415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,948 control chromosomes in the GnomAD database, including 15,382 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 0.44 (15382 hom., cov: 31)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP1	NM_006129.5	c.2107+415C>T		intron_variant	Intron 15 of 19	ENST00000306385.10	NP_006120.1
BMP1	NM_001199.4	c.2107+415C>T		intron_variant	Intron 15 of 15	ENST00000306349.13	NP_001190.1
BMP1	NR_033403.2	n.2178+415C>T		intron_variant	Intron 15 of 19
BMP1	NR_033404.2	n.2178+415C>T		intron_variant	Intron 15 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.2107+415C>T		intron_variant	Intron 15 of 19	1	NM_006129.5	ENSP00000305714.5
BMP1	ENST00000306349.13	c.2107+415C>T		intron_variant	Intron 15 of 15	1	NM_001199.4	ENSP00000306121.8

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66680 AN: 151830 Hom.: 15371 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.439 AC: 66697 AN: 151948 Hom.: 15382 Cov.: 31 AF XY: 0.435 AC XY: 32304 AN XY: 74260

African (AFR) AF: 0.313 AC: 12981 AN: 41430

American (AMR) AF: 0.426 AC: 6506 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1484 AN: 5154

South Asian (SAS) AF: 0.463 AC: 2230 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4588 AN: 10564

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35709 AN: 67934

Other (OTH) AF: 0.425 AC: 899 AN: 2114

Alfa AF: 0.498 Hom.: 32575

Bravo AF: 0.433

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.55
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3857979; hg19: chr8-22055348;