rs230188

chr20-57195460-T-C

Variant summary

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

The NM_001719.3(BMP7):c.760+7015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,128 control chromosomes in the GnomAD database, including 32,660 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 0.64 (32660 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

Genes affected

BMP7 (HGNC:1074): (bone morphogenetic protein 7) 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, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.760+7015A>G		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.760+7015A>G		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97525 AN: 152010 Hom.: 32611 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.642 AC: 97645 AN: 152128 Hom.: 32660 Cov.: 33 AF XY: 0.640 AC XY: 47611 AN XY: 74374

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.631

Alfa AF: 0.589 Hom.: 13288

Bravo AF: 0.651

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.1
Dann	Benign	0.56

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: rs230188; hg19: chr20-55770516;