6-55830578-A-G

Variant names:

• chr6-55830578-A-G
• rs17734678
• NM_021073.4:c.491-10731T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021073.4(BMP5):​c.491-10731T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,044 control chromosomes in the GnomAD database, including 3,132 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 0.18 (3132 hom., cov: 32)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021073.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	NM_021073.4	MANE Select	c.491-10731T>C		intron	N/A	NP_066551.1
	BMP5	NM_001329754.2		c.491-10731T>C		intron	N/A	NP_001316683.1
	BMP5	NM_001329756.2		c.491-10731T>C		intron	N/A	NP_001316685.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP5	ENST00000370830.4	TSL:1 MANE Select	c.491-10731T>C		intron	N/A	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27480 AN: 151926 Hom.: 3121 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.181 AC: 27495 AN: 152044 Hom.: 3132 Cov.: 32 AF XY: 0.179 AC XY: 13330 AN XY: 74298

African (AFR) AF: 0.0489 AC: 2030 AN: 41520

American (AMR) AF: 0.169 AC: 2568 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3470

East Asian (EAS) AF: 0.125 AC: 644 AN: 5172

South Asian (SAS) AF: 0.189 AC: 911 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2638 AN: 10574

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17194 AN: 67934

Other (OTH) AF: 0.205 AC: 433 AN: 2116

Alfa AF: 0.155 Hom.: 396

Bravo AF: 0.169

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.75
PhyloP100		1.9
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: rs17734678; hg19: chr6-55695376;