Variant rs2148328 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001719.3(BMP7):c.1146+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,564,692 control chromosomes in the GnomAD database, including 184,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 15181 hom., cov: 33)

Exomes 𝑓: 0.48 ( 169767 hom. )

Consequence

BMP7
NM_001719.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1827637E-6).

BP6

Variant 20-57173150-G-A is Benign according to our data. Variant chr20-57173150-G-A is described in ClinVar as [Benign]. Clinvar id is 1242634.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3 linkuse as main transcript	c.1146+50C>T		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8 linkuse as main transcript	c.1146+50C>T		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65091

AN:

151898

Hom.:

15191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.434

GnomAD3 exomes

AF:

0.468

AC:

111568

AN:

238210

Hom.:

27414

AF XY:

0.467

AC XY:

60111

AN XY:

128776

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.697

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.501

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.485

AC:

684705

AN:

1412676

Hom.:

169767

Cov.:

AF XY:

0.481

AC XY:

338766

AN XY:

704670

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.419

Gnomad4 EAS exome

AF:

0.664

Gnomad4 SAS exome

AF:

0.336

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.499

Gnomad4 OTH exome

AF:

0.465

GnomAD4 genome

AF:

0.428

AC:

65080

AN:

152016

Hom.:

15181

Cov.:

AF XY:

0.432

AC XY:

32090

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.422

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.456

Hom.:

7103

Bravo

AF:

0.412

TwinsUK

AF:

0.491

AC:

1822

ALSPAC

AF:

0.496

AC:

1911

ESP6500AA

AF:

0.249

AC:

1096

ESP6500EA

AF:

0.504

AC:

4335

ExAC

AF:

0.456

AC:

55264

Asia WGS

AF:

0.449

AC:

1559

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

Cadd

Benign

0.016

Dann

Benign

0.62

DEOGEN2

Benign

0.23

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0000032

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

2.4

REVEL

Benign

0.091

Sift

Benign

0.46

Polyphen

0.0

Vest4

0.024

ClinPred

0.015

GERP RS

-7.7

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