NM_021073.4:c.491-26566C>T

Variant names:

• chr6-55846413-G-A
• rs1470527
• NM_021073.4:c.491-26566C>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.491-26566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,752 control chromosomes in the GnomAD database, including 16,237 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 0.45 (16237 hom., cov: 32)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.491-26566C>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.491-26566C>T		intron_variant	Intron 1 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68254 AN: 151634 Hom.: 16194 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.450 AC: 68358 AN: 151752 Hom.: 16237 Cov.: 32 AF XY: 0.446 AC XY: 33070 AN XY: 74146

African (AFR) AF: 0.599 AC: 24796 AN: 41424

American (AMR) AF: 0.416 AC: 6334 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1588 AN: 3460

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5166

South Asian (SAS) AF: 0.382 AC: 1836 AN: 4812

European-Finnish (FIN) AF: 0.364 AC: 3839 AN: 10550

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27023 AN: 67798

Other (OTH) AF: 0.456 AC: 961 AN: 2108

Alfa AF: 0.418 Hom.: 43157

Bravo AF: 0.460

Asia WGS AF: 0.392 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.61
PhyloP100		1.7
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: rs1470527; hg19: chr6-55711211;