8-22210261-T-G

Position:

• chr8-22210261-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.2826+566T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,966 control chromosomes in the GnomAD database, including 8,047 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 0.30 (8047 hom., cov: 32)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP1	NM_006129.5	c.2826+566T>G		intron_variant		ENST00000306385.10	NP_006120.1
BMP1	NR_033403.2	n.2897+566T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.2826+566T>G		intron_variant		1	NM_006129.5	ENSP00000305714.5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45169 AN: 151852 Hom.: 8041 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.298 AC: 45217 AN: 151966 Hom.: 8047 Cov.: 32 AF XY: 0.290 AC XY: 21555 AN XY: 74234

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.263

Alfa AF: 0.250 Hom.: 6170

Bravo AF: 0.306

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.49

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: rs4076873; hg19: chr8-22067774;