Genetic Variant BMP7:c.*2212G>A (chr20-57168747-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001719.3(BMP7):c.*2212G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,076 control chromosomes in the GnomAD database, including 15,160 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 0.43 ( 15158 hom., cov: 32)

Exomes 𝑓: 0.39 ( 2 hom. )

Consequence

BMP7
NM_001719.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Variant links:

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]

BMP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.*2212G>A		downstream_gene_variant		ENST00000395863.8	NP_001710.1	P18075A8K571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 link	c.*2212G>A		downstream_gene_variant		1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65425

AN:

151940

Hom.:

15160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.427

GnomAD4 exome

AF:

0.389

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.430

AC:

65432

AN:

152058

Hom.:

15158

Cov.:

AF XY:

0.433

AC XY:

32168

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.452

Hom.:

5140

Bravo

AF:

0.418

Asia WGS

AF:

0.434

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over