rs9382564

Variant names:

• chr6-55873715-G-T
• rs9382564
• NM_021073.4:c.490+661C>A

Variant summary

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

The NM_021073.4(BMP5):​c.490+661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 151,772 control chromosomes in the GnomAD database, including 190 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 0.036 (190 hom., cov: 32)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 publications found

Genes affected

BMP5 (HGNC:1072): (bone morphogenetic protein 5) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

BMP5 Gene-Disease associations (from GenCC):

• dysostosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.490+661C>A		intron_variant	Intron 1 of 6	ENST00000370830.4	NP_066551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4	c.490+661C>A		intron_variant	Intron 1 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5483 AN: 151652 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.00798

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0329

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0346

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

GnomAD4 genome AF: 0.0362 AC: 5488 AN: 151772 Hom.: 190 Cov.: 32 AF XY: 0.0370 AC XY: 2745 AN XY: 74136

African (AFR) AF: 0.00796 AC: 330 AN: 41474

American (AMR) AF: 0.0565 AC: 861 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3468

East Asian (EAS) AF: 0.160 AC: 821 AN: 5144

South Asian (SAS) AF: 0.0904 AC: 435 AN: 4810

European-Finnish (FIN) AF: 0.0191 AC: 201 AN: 10532

Middle Eastern (MID) AF: 0.0317 AC: 9 AN: 284

European-Non Finnish (NFE) AF: 0.0393 AC: 2664 AN: 67810

Other (OTH) AF: 0.0361 AC: 76 AN: 2104

Alfa AF: 0.0403 Hom.: 20

Bravo AF: 0.0370

Asia WGS AF: 0.113 AC: 390 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.61
PhyloP100		-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: rs9382564; hg19: chr6-55738513;