rs9475431

chr6-55850396-C-Achr6-55850396-C-T

Variant summary

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

The NM_021073.4(BMP5):c.490+23980G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 97,088 control chromosomes in the GnomAD database, including 2,842 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 0.28 (2842 hom., cov: 23)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP5	NM_021073.4	c.490+23980G>T		intron_variant		ENST00000370830.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP5	ENST00000370830.4	c.490+23980G>T		intron_variant		1	NM_021073.4	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 27560 AN: 97016 Hom.: 2831 Cov.: 23

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.284 AC: 27612 AN: 97088 Hom.: 2842 Cov.: 23 AF XY: 0.279 AC XY: 13290 AN XY: 47560

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.285

Alfa AF: 0.143 Hom.: 170

Bravo AF: 0.410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.41
Dann	Benign	0.73

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: rs9475431; hg19: chr6-55715194;