chr4-81035770-T-C

Variant names:

• chr4-81035770-T-C
• rs1994990
• NM_001201.5:c.316+4170T>C

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+4170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,798 control chromosomes in the GnomAD database, including 40,023 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 0.69 (40023 hom., cov: 30)
• Consequence: BMP3 NM_001201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 5 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=-0.9).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP3	NM_001201.5	MANE Select	c.316+4170T>C		intron	N/A	NP_001192.4	P12645

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP3	ENST00000282701.4	TSL:1 MANE Select	c.316+4170T>C		intron	N/A	ENSP00000282701.2	P12645
	BMP3	ENST00000909109.1		c.316+4170T>C		intron	N/A	ENSP00000579168.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104541 AN: 151680 Hom.: 40009 Cov.: 30

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.685

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: 0.700

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

GnomAD4 genome AF: 0.689 AC: 104569 AN: 151798 Hom.: 40023 Cov.: 30 AF XY: 0.691 AC XY: 51307 AN XY: 74204

African (AFR) AF: 0.321 AC: 13308 AN: 41430

American (AMR) AF: 0.782 AC: 11914 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2370 AN: 3458

East Asian (EAS) AF: 0.810 AC: 4184 AN: 5166

South Asian (SAS) AF: 0.822 AC: 3950 AN: 4808

European-Finnish (FIN) AF: 0.823 AC: 8697 AN: 10568

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

European-Non Finnish (NFE) AF: 0.851 AC: 57699 AN: 67810

Other (OTH) AF: 0.702 AC: 1484 AN: 2114

Alfa AF: 0.807 Hom.: 26120

Bravo AF: 0.667

Asia WGS AF: 0.779 AC: 2709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.37
PhyloP100		0.025
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: rs1994990; hg19: chr4-81956924;