chr20-57175004-T-C

Position:

chr20-57175004-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001719.3(BMP7):c.962A>G(p.Asn321Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00363 in 1,610,820 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 43 hom. )

Consequence

BMP7
NM_001719.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00505054).

BP6

Variant 20-57175004-T-C is Benign according to our data. Variant chr20-57175004-T-C is described in ClinVar as [Benign]. Clinvar id is 771049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-57175004-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00343 (523/152332) while in subpopulation SAS AF= 0.0203 (98/4832). AF 95% confidence interval is 0.017. There are 1 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 523 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3 linkuse as main transcript	c.962A>G	p.Asn321Ser	missense_variant	5/7	ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8 linkuse as main transcript	c.962A>G	p.Asn321Ser	missense_variant	5/7	1	NM_001719.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00279

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00537

AC:

1332

AN:

248000

Hom.:

AF XY:

0.00622

AC XY:

835

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.00467

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.000305

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00870

GnomAD4 exome

AF:

0.00365

AC:

5330

AN:

1458488

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2982

AN XY:

725600

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.0161

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0179

Gnomad4 FIN exome

AF:

0.000237

Gnomad4 NFE exome

AF:

0.00241

Gnomad4 OTH exome

AF:

0.00507

GnomAD4 genome

AF:

0.00343

AC:

523

AN:

152332

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00279

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00537

AC:

652

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00529

EpiControl

AF:

0.00517

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

BMP7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 24, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Congenital total pulmonary venous return anomaly

Benign:1

Benign, no assertion criteria provided

case-control

Cytogenetics- Mohapatra Lab, Banaras Hindu University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Uncertain

0.46

T;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

D;T;D

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.87

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.20

MVP

0.73

MPC

0.54

ClinPred

0.0060

GERP RS

4.0

Varity_R

0.083

gMVP

0.54

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