rs3789334

Positions:

• chr20-6772275-G-A
• chr20-6772275-G-T

Variant summary

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

The NM_001200.4(BMP2):​c.346+1803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,052 control chromosomes in the GnomAD database, including 6,569 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 0.29 (6569 hom., cov: 33)
• Consequence: BMP2 NM_001200.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

Genes affected

BMP2 (HGNC:1069): (bone morphogenetic protein 2) 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, which plays a role in bone and cartilage development. Duplication of a regulatory region downstream of this gene causes a form of brachydactyly characterized by a malformed index finger and second toe in human patients. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2	NM_001200.4	c.346+1803G>A		intron_variant		ENST00000378827.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2	ENST00000378827.5	c.346+1803G>A		intron_variant		1	NM_001200.4	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43903 AN: 151934 Hom.: 6573 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43908 AN: 152052 Hom.: 6569 Cov.: 33 AF XY: 0.284 AC XY: 21100 AN XY: 74314

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.296

Alfa AF: 0.153 Hom.: 287

Bravo AF: 0.293

Asia WGS AF: 0.209 AC: 725 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
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: rs3789334; hg19: chr20-6752922;