4-81038812-A-G

Position:

• chr4-81038812-A-G

Variant summary

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

The NM_001201.5(BMP3):​c.317-6926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,118 control chromosomes in the GnomAD database, including 31,659 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 0.59 (31659 hom., cov: 32)
• Consequence: BMP3 NM_001201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

Genes affected

BMP3 (HGNC:1070): (bone morphogenetic protein 3) 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. This protein suppresses osteoblast differentiation, and negatively regulates bone density, by modulating TGF-beta receptor availability to other ligands. [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 (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP3	NM_001201.5	c.317-6926A>G		intron_variant		ENST00000282701.4	NP_001192.4
BMP3	XM_006714291.4	c.317-6926A>G		intron_variant			XP_006714354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP3	ENST00000282701.4	c.317-6926A>G		intron_variant		1	NM_001201.5	ENSP00000282701.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90207 AN: 152000 Hom.: 31644 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.593 AC: 90236 AN: 152118 Hom.: 31659 Cov.: 32 AF XY: 0.593 AC XY: 44099 AN XY: 74368

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.606

Alfa AF: 0.688 Hom.: 4872

Bravo AF: 0.569

Asia WGS AF: 0.564 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.50

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: rs5022942; hg19: chr4-81959966;