chr4-81047179-T-A

Position:

• chr4-81047179-T-A

Variant summary

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

The NM_001201.5(BMP3):​c.1227+531T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,124 control chromosomes in the GnomAD database, including 40,524 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 0.71 (40524 hom., cov: 32)
• Consequence: BMP3 NM_001201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP3	NM_001201.5	c.1227+531T>A		intron_variant		ENST00000282701.4
BMP3	XM_006714291.4	c.1128+630T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP3	ENST00000282701.4	c.1227+531T>A		intron_variant		1	NM_001201.5	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107705 AN: 152006 Hom.: 40507 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.708 AC: 107753 AN: 152124 Hom.: 40524 Cov.: 32 AF XY: 0.710 AC XY: 52777 AN XY: 74364

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.711

Alfa AF: 0.775 Hom.: 5887

Bravo AF: 0.688

Asia WGS AF: 0.674 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.72

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: rs2903746; hg19: chr4-81968333;