chr4-81032591-G-A

Variant names:

• chr4-81032591-G-A
• rs1106107
• NM_001201.5:c.316+991G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201.5(BMP3):​c.316+991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,176 control chromosomes in the GnomAD database, including 39,676 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 0.68 (39676 hom., cov: 33)
• Consequence: BMP3 NM_001201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP3	NM_001201.5	MANE Select	c.316+991G>A		intron	N/A	NP_001192.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP3	ENST00000282701.4	TSL:1 MANE Select	c.316+991G>A		intron	N/A	ENSP00000282701.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103316 AN: 152058 Hom.: 39662 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.679 AC: 103343 AN: 152176 Hom.: 39676 Cov.: 33 AF XY: 0.682 AC XY: 50739 AN XY: 74392

African (AFR) AF: 0.287 AC: 11924 AN: 41502

American (AMR) AF: 0.777 AC: 11881 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2376 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4192 AN: 5172

South Asian (SAS) AF: 0.821 AC: 3964 AN: 4826

European-Finnish (FIN) AF: 0.823 AC: 8722 AN: 10598

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57847 AN: 68002

Other (OTH) AF: 0.699 AC: 1474 AN: 2110

Alfa AF: 0.771 Hom.: 79385

Bravo AF: 0.656

Asia WGS AF: 0.774 AC: 2691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.38
PhyloP100		0.22
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: rs1106107; hg19: chr4-81953745;