rs921126

Variant names:

• chr6-55844943-C-T
• rs921126
• NM_021073.4:c.491-25096G>A

Variant summary

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

The NM_021073.4(BMP5):​c.491-25096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,774 control chromosomes in the GnomAD database, including 3,172 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 0.19 (3172 hom., cov: 33)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.491-25096G>A		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.491-25096G>A		intron_variant	Intron 1 of 6	1	NM_021073.4	ENSP00000359866.3

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28623 AN: 151656 Hom.: 3159 Cov.: 33

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.189 AC: 28650 AN: 151774 Hom.: 3172 Cov.: 33 AF XY: 0.186 AC XY: 13834 AN XY: 74180

African (AFR) AF: 0.0960 AC: 3981 AN: 41482

American (AMR) AF: 0.147 AC: 2246 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3466

East Asian (EAS) AF: 0.0475 AC: 246 AN: 5182

South Asian (SAS) AF: 0.181 AC: 873 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2642 AN: 10536

Middle Eastern (MID) AF: 0.184 AC: 52 AN: 282

European-Non Finnish (NFE) AF: 0.253 AC: 17160 AN: 67762

Other (OTH) AF: 0.208 AC: 438 AN: 2104

Alfa AF: 0.225 Hom.: 508

Bravo AF: 0.175

Asia WGS AF: 0.150 AC: 517 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.46
PhyloP100		-0.47
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: rs921126; hg19: chr6-55709741;