rs921126

Positions:

• chr6-55844943-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.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

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=-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/exons	MANE	UniProt
BMP5	NM_021073.4	c.491-25096G>A		intron_variant		ENST00000370830.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP5	ENST00000370830.4	c.491-25096G>A		intron_variant		1	NM_021073.4	P1

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

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.208

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

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: rs921126; hg19: chr6-55709741;