4-81047333-T-C

Variant names:

• chr4-81047333-T-C
• rs10516736
• NM_001201.5:c.1227+685T>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.1227+685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,166 control chromosomes in the GnomAD database, including 1,337 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 0.12 (1337 hom., cov: 31)
• Consequence: BMP3 NM_001201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP3	NM_001201.5	c.1227+685T>C		intron_variant	Intron 2 of 2	ENST00000282701.4	NP_001192.4
BMP3	XM_006714291.4	c.1128+784T>C		intron_variant	Intron 2 of 2		XP_006714354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP3	ENST00000282701.4	c.1227+685T>C		intron_variant	Intron 2 of 2	1	NM_001201.5	ENSP00000282701.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18640 AN: 152048 Hom.: 1333 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0481

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.123 AC: 18664 AN: 152166 Hom.: 1337 Cov.: 31 AF XY: 0.119 AC XY: 8878 AN XY: 74408

African (AFR) AF: 0.188 AC: 7796 AN: 41490

American (AMR) AF: 0.106 AC: 1621 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3468

East Asian (EAS) AF: 0.0481 AC: 249 AN: 5182

South Asian (SAS) AF: 0.110 AC: 529 AN: 4816

European-Finnish (FIN) AF: 0.0442 AC: 469 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0985 AC: 6695 AN: 67992

Other (OTH) AF: 0.139 AC: 294 AN: 2112

Alfa AF: 0.108 Hom.: 790

Bravo AF: 0.132

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.33
PhyloP100		0.35
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: rs10516736; hg19: chr4-81968487;