rs61733438

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
hypospadias
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BMP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 771049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 523 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.962A>G	p.Asn321Ser	missense	Exon 5 of 7	NP_001710.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BMP7	ENST00000395863.8	TSL:1 MANE Select	c.962A>G	p.Asn321Ser	missense	Exon 5 of 7	ENSP00000379204.3
BMP7	ENST00000450594.6	TSL:2	c.962A>G	p.Asn321Ser	missense	Exon 5 of 6	ENSP00000398687.2
BMP7	ENST00000395864.7	TSL:5	c.764A>G	p.Asn255Ser	missense	Exon 4 of 6	ENSP00000379205.3

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

GnomAD2 exomes

AF:

0.00537

AC:

1332

AN:

248000

AF XY:

0.00622

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 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

African (AFR)

AF:

0.00114

AC:

AN:

33462

American (AMR)

AF:

0.00481

AC:

215

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

420

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39682

South Asian (SAS)

AF:

0.0179

AC:

1542

AN:

85990

European-Finnish (FIN)

AF:

0.000237

AC:

AN:

50712

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5768

European-Non Finnish (NFE)

AF:

0.00241

AC:

2681

AN:

1111744

Other (OTH)

AF:

0.00507

AC:

306

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

327

653

980

1306

1633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00343

AC:

523

AN:

152332

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41576

American (AMR)

AF:

0.00836

AC:

128

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0203

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00279

AC:

190

AN:

68028

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00355

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

BMP7-related disorder (1)

Congenital total pulmonary venous return anomaly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.31

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

PhyloP100

3.8

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.87

REVEL

Benign

0.18

Sift

Benign

0.74

Sift4G

Benign

0.76

Polyphen

0.0

Vest4

0.20

MVP

0.73

MPC

0.54

ClinPred

0.0060

GERP RS

4.0

Varity_R

0.083

gMVP

0.54

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over