Genetic Variant BMP7:c.*334T>C (chr20-57170625-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001719.3(BMP7):c.*334T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 352,400 control chromosomes in the GnomAD database, including 40,508 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 0.45 ( 16205 hom., cov: 32)

Exomes 𝑓: 0.48 ( 24303 hom. )

Consequence

BMP7
NM_001719.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.287

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.*334T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000395863.8	NP_001710.1	P18075A8K571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 link	c.*334T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001719.3	ENSP00000379204.3		P18075
BMP7	ENST00000395864.7 link	c.*334T>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000379205.3		B1AKZ9

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67666

AN:

151886

Hom.:

16207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.480

AC:

96247

AN:

200396

Hom.:

24303

Cov.:

AF XY:

0.465

AC XY:

50340

AN XY:

108264

show subpopulations

African (AFR)

AF:

0.264

AC:

1505

AN:

5704

American (AMR)

AF:

0.412

AC:

4053

AN:

9830

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

2171

AN:

4900

East Asian (EAS)

AF:

0.684

AC:

6012

AN:

8784

South Asian (SAS)

AF:

0.337

AC:

12653

AN:

37544

European-Finnish (FIN)

AF:

0.578

AC:

5421

AN:

9382

Middle Eastern (MID)

AF:

0.454

AC:

329

AN:

724

European-Non Finnish (NFE)

AF:

0.522

AC:

59257

AN:

113496

Other (OTH)

AF:

0.483

AC:

4846

AN:

10032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2358

4716

7074

9432

11790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.445

AC:

67672

AN:

152004

Hom.:

16205

Cov.:

AF XY:

0.447

AC XY:

33240

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.267

AC:

11062

AN:

41424

American (AMR)

AF:

0.433

AC:

6618

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1492

AN:

3472

East Asian (EAS)

AF:

0.681

AC:

3520

AN:

5170

South Asian (SAS)

AF:

0.347

AC:

1667

AN:

4808

European-Finnish (FIN)

AF:

0.590

AC:

6233

AN:

10570

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35336

AN:

67964

Other (OTH)

AF:

0.443

AC:

936

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.482

Hom.:

18885

Bravo

AF:

0.432

Asia WGS

AF:

0.441

AC:

1530

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

DANN

Benign

0.53

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over