rs3798821

chr6-55873454-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021073.4(BMP5):c.490+922A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 151,886 control chromosomes in the GnomAD database, including 301 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 0.058 (301 hom., cov: 32)
• Consequence: BMP5 NM_021073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP5	NM_021073.4	c.490+922A>C		intron_variant		ENST00000370830.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP5	ENST00000370830.4	c.490+922A>C		intron_variant		1	NM_021073.4	P1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8805 AN: 151762 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0694

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0575

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

GnomAD4 genome AF: 0.0580 AC: 8812 AN: 151886 Hom.: 301 Cov.: 32 AF XY: 0.0578 AC XY: 4289 AN XY: 74198

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0978

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.0603

Gnomad4 FIN AF: 0.0508

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0536 Hom.: 27

Bravo AF: 0.0606

Asia WGS AF: 0.0560 AC: 191 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.9
Dann	Benign	0.75

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: rs3798821; hg19: chr6-55738252;