6-55762301-A-G

Variant names:

• chr6-55762301-A-G
• rs228137
• NM_021073.4:c.1028-1768T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021073.4(BMP5):​c.1028-1768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,076 control chromosomes in the GnomAD database, including 2,339 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 0.16 (2339 hom., cov: 32)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 0 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 (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.1028-1768T>C		intron_variant	Intron 4 of 6	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2	c.1028-1768T>C		intron_variant	Intron 4 of 5		NP_001316683.1
BMP5	NM_001329756.2	c.1028-6619T>C		intron_variant	Intron 4 of 4		NP_001316685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4	c.1028-1768T>C		intron_variant	Intron 4 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24854 AN: 151958 Hom.: 2340 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.163 AC: 24861 AN: 152076 Hom.: 2339 Cov.: 32 AF XY: 0.169 AC XY: 12537 AN XY: 74318

African (AFR) AF: 0.106 AC: 4416 AN: 41522

American (AMR) AF: 0.212 AC: 3228 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3466

East Asian (EAS) AF: 0.160 AC: 826 AN: 5150

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2550 AN: 10560

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11125 AN: 67978

Other (OTH) AF: 0.151 AC: 319 AN: 2108

Alfa AF: 0.168 Hom.: 770

Bravo AF: 0.157

Asia WGS AF: 0.232 AC: 802 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		0.078
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: rs228137; hg19: chr6-55627099;