NM_001719.3:c.761-1592A>G

Variant names:

• chr20-57185511-T-C
• rs6064508
• NM_001719.3:c.761-1592A>G

Variant summary

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

The NM_001719.3(BMP7):​c.761-1592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,216 control chromosomes in the GnomAD database, including 7,185 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 (7185 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.761-1592A>G		intron_variant	Intron 3 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.761-1592A>G		intron_variant	Intron 3 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44409 AN: 152098 Hom.: 7184 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.292 AC: 44430 AN: 152216 Hom.: 7185 Cov.: 33 AF XY: 0.292 AC XY: 21735 AN XY: 74424

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.313

Alfa AF: 0.361 Hom.: 20794

Bravo AF: 0.280

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.58

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: rs6064508; hg19: chr20-55760567;