rs3798821

Variant names:

• chr6-55873454-T-G
• rs3798821
• NM_021073.4:c.490+922A>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.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
• Publications: 2 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=-0.8).
• 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 rank	MANE	Protein	UniProt
BMP5	NM_021073.4	c.490+922A>C		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.490+922A>C		intron_variant	Intron 1 of 6	1	NM_021073.4	ENSP00000359866.3

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

African (AFR) AF: 0.0550 AC: 2285 AN: 41526

American (AMR) AF: 0.0978 AC: 1488 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.0710 AC: 366 AN: 5154

South Asian (SAS) AF: 0.0603 AC: 291 AN: 4822

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10608

Middle Eastern (MID) AF: 0.0746 AC: 20 AN: 268

European-Non Finnish (NFE) AF: 0.0501 AC: 3400 AN: 67800

Other (OTH) AF: 0.0569 AC: 120 AN: 2110

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
PhyloP100		-0.14
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: rs3798821; hg19: chr6-55738252;