rs2855532

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001202.6(BMP4):c.-8+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 396,242 control chromosomes in the GnomAD database, including 36,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12845 hom., cov: 31)

Exomes 𝑓: 0.43 ( 23211 hom. )

Consequence

BMP4
NM_001202.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.87

Publications

14 publications found

Variant links:

Genes affected

BMP4 (HGNC:1071): (bone morphogenetic protein 4) 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. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

BMP4 Gene-Disease associations (from GenCC):

BMP4-related ocular growth disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
microphthalmia with brain and digit anomalies
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Stickler syndrome
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
orofacial cleft 11
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

BMP4 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 (BayesDel_noAF=-0.82).

BP6

Variant 14-53953247-G-A is Benign according to our data. Variant chr14-53953247-G-A is described in ClinVar as Benign. ClinVar VariationId is 1192499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP4	NM_001202.6	MANE Select	c.-8+29C>T	intron	N/A	NP_001193.2	P12644
BMP4	NM_001347912.1		c.187+29C>T	intron	N/A	NP_001334841.1
BMP4	NM_001347914.2		c.-8+29C>T	intron	N/A	NP_001334843.1	P12644

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP4	ENST00000245451.9	TSL:1 MANE Select	c.-8+29C>T	intron	N/A	ENSP00000245451.4	P12644
BMP4	ENST00000558984.1	TSL:1	c.-8+29C>T	intron	N/A	ENSP00000454134.1	P12644
BMP4	ENST00000559087.5	TSL:1	c.-8+29C>T	intron	N/A	ENSP00000453485.1	P12644

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61562

AN:

151776

Hom.:

12842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.434

AC:

106107

AN:

244348

Hom.:

23211

Cov.:

AF XY:

0.434

AC XY:

53791

AN XY:

123966

show subpopulations

African (AFR)

AF:

0.306

AC:

2180

AN:

7114

American (AMR)

AF:

0.479

AC:

3531

AN:

7364

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

3432

AN:

9142

East Asian (EAS)

AF:

0.423

AC:

9634

AN:

22784

South Asian (SAS)

AF:

0.459

AC:

1343

AN:

2924

European-Finnish (FIN)

AF:

0.452

AC:

9519

AN:

21076

Middle Eastern (MID)

AF:

0.354

AC:

455

AN:

1284

European-Non Finnish (NFE)

AF:

0.441

AC:

68955

AN:

156468

Other (OTH)

AF:

0.436

AC:

7058

AN:

16192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2823

5647

8470

11294

14117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.406

AC:

61606

AN:

151894

Hom.:

12845

Cov.:

AF XY:

0.406

AC XY:

30110

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.302

AC:

12513

AN:

41440

American (AMR)

AF:

0.445

AC:

6794

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1273

AN:

3468

East Asian (EAS)

AF:

0.469

AC:

2405

AN:

5126

South Asian (SAS)

AF:

0.478

AC:

2301

AN:

4810

European-Finnish (FIN)

AF:

0.447

AC:

4719

AN:

10564

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.445

AC:

30204

AN:

67896

Other (OTH)

AF:

0.408

AC:

861

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1823

3646

5470

7293

9116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.437

Hom.:

8787

Bravo

AF:

0.405

Asia WGS

AF:

0.446

AC:

1549

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microphthalmia with brain and digit anomalies (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.9

PromoterAI

-0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over