rs11775186

Positions:

• chr8-22200609-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006129.5(BMP1):​c.2108-1194T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,124 control chromosomes in the GnomAD database, including 637 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 0.089 (637 hom., cov: 32)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP1	NM_001199.4	c.2108-509T>G		intron_variant		ENST00000306349.13
BMP1	NM_006129.5	c.2108-1194T>G		intron_variant		ENST00000306385.10
BMP1	NR_033403.2	n.2179-1194T>G		intron_variant, non_coding_transcript_variant
BMP1	NR_033404.2	n.2179-509T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP1	ENST00000306349.13	c.2108-509T>G		intron_variant		1	NM_001199.4
BMP1	ENST00000306385.10	c.2108-1194T>G		intron_variant		1	NM_006129.5	P1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13540 AN: 152006 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0890 AC: 13542 AN: 152124 Hom.: 637 Cov.: 32 AF XY: 0.0883 AC XY: 6564 AN XY: 74368

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.0818

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.0915

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0897 Hom.: 848

Bravo AF: 0.0875

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.053
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11775186; hg19: chr8-22058122;