rs9475429

Positions:

• chr6-55850304-T-A

Variant summary

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

The NM_021073.4(BMP5):​c.490+24072A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,736 control chromosomes in the GnomAD database, including 12,975 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 0.40 (12975 hom., cov: 31)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP5	NM_021073.4	c.490+24072A>T		intron_variant		ENST00000370830.4	NP_066551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4	c.490+24072A>T		intron_variant		1	NM_021073.4	ENSP00000359866	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61196 AN: 151618 Hom.: 12944 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.404 AC: 61281 AN: 151736 Hom.: 12975 Cov.: 31 AF XY: 0.397 AC XY: 29459 AN XY: 74156

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.417

Alfa AF: 0.400 Hom.: 1535

Bravo AF: 0.409

Asia WGS AF: 0.258 AC: 895 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs9475429; hg19: chr6-55715102;