dbSNP rs6025416: BMP7:c.*1111A>G (chr20-57169848-T-C) – 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.*1111A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,504 control chromosomes in the GnomAD database, including 15,117 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 0.43 ( 15117 hom., cov: 31)

Exomes 𝑓: 0.47 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

BMP7
NM_001719.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

1 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.*1111A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 link	c.*1111A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65433

AN:

151384

Hom.:

15117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.429

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.475

AC:

AN:

Hom.:

Cov.:

AF XY:

0.429

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.536

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.432

AC:

65444

AN:

151504

Hom.:

15117

Cov.:

AF XY:

0.434

AC XY:

32101

AN XY:

73988

show subpopulations

African (AFR)

AF:

0.262

AC:

10844

AN:

41378

American (AMR)

AF:

0.421

AC:

6410

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1454

AN:

3466

East Asian (EAS)

AF:

0.675

AC:

3448

AN:

5110

South Asian (SAS)

AF:

0.333

AC:

1602

AN:

4806

European-Finnish (FIN)

AF:

0.571

AC:

5984

AN:

10476

Middle Eastern (MID)

AF:

0.400

AC:

116

AN:

290

European-Non Finnish (NFE)

AF:

0.503

AC:

34097

AN:

67734

Other (OTH)

AF:

0.425

AC:

897

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1790

3580

5369

7159

8949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.285

Hom.:

701

Bravo

AF:

0.421

Asia WGS

AF:

0.434

AC:

1506

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.99

(source)

DANN

Benign

0.25

PhyloP100

-1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over