rs1005464

chr20-6775501-G-A

Variant summary

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

The NM_001200.4(BMP2):c.347-2744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,904 control chromosomes in the GnomAD database, including 3,264 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 0.20 (3264 hom., cov: 32)
• Consequence: BMP2 NM_001200.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2	NM_001200.4	c.347-2744G>A		intron_variant		ENST00000378827.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2	ENST00000378827.5	c.347-2744G>A		intron_variant		1	NM_001200.4	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29940 AN: 151786 Hom.: 3258 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.197 AC: 29959 AN: 151904 Hom.: 3264 Cov.: 32 AF XY: 0.199 AC XY: 14795 AN XY: 74232

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.213

Alfa AF: 0.219 Hom.: 5388

Bravo AF: 0.192

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.53

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: rs1005464; hg19: chr20-6756148;