Variant rs112344257 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001719.3(BMP7):c.752C>T(p.Thr251Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,604,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

BMP7
NM_001719.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

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:

BMP7 (HGNC:):

BMP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15888783).

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3 linkuse as main transcript	c.752C>T	p.Thr251Met	missense_variant	3/7	ENST00000395863.8	NP_001710.1	P18075A8K571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 linkuse as main transcript	c.752C>T	p.Thr251Met	missense_variant	3/7	1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.000331

AC:

AN:

150862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000547

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000288

AC:

AN:

242912

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

132186

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000429

AC:

623

AN:

1453146

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

303

AN XY:

723234

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000664

Gnomad4 NFE exome

AF:

0.000511

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000331

AC:

AN:

150980

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

73738

show subpopulations

Gnomad4 AFR

AF:

0.000146

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000547

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital anomaly of kidney and urinary tract

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.081

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.48

P;D;P

Vest4

0.49

MVP

0.63

MPC

1.5

ClinPred

0.29

GERP RS

3.7

Varity_R

0.20

gMVP

0.49

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over