rs9475430

Variant names:

• chr6-55850354-G-A
• rs9475430
• NM_021073.4:c.490+24022C>T

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+24022C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.035 (40 hom., cov: 15)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.490+24022C>T		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+24022C>T		intron_variant	Intron 1 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 2916 AN: 83138 Hom.: 40 Cov.: 15

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.00559

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.00772

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0336

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

GnomAD4 genome AF: 0.0351 AC: 2923 AN: 83174 Hom.: 40 Cov.: 15 AF XY: 0.0339 AC XY: 1394 AN XY: 41138

African (AFR) AF: 0.0890 AC: 1759 AN: 19766

American (AMR) AF: 0.0242 AC: 218 AN: 9026

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 61 AN: 1774

East Asian (EAS) AF: 0.00774 AC: 33 AN: 4266

South Asian (SAS) AF: 0.0203 AC: 67 AN: 3300

European-Finnish (FIN) AF: 0.0132 AC: 83 AN: 6270

Middle Eastern (MID) AF: 0.0135 AC: 2 AN: 148

European-Non Finnish (NFE) AF: 0.0178 AC: 661 AN: 37162

Other (OTH) AF: 0.0335 AC: 37 AN: 1104

Alfa AF: 0.381 Hom.: 13725

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-1.0
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: rs9475430; hg19: chr6-55715152; COSMIC: COSV63705309;