chr14-53952268-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001202.6(BMP4):c.-7-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,603,892 control chromosomes in the GnomAD database, including 712,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 55507 hom., cov: 30)

Exomes 𝑓: 0.95 ( 657440 hom. )

Consequence

BMP4
NM_001202.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.673

Publications

11 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 14-53952268-T-C is Benign according to our data. Variant chr14-53952268-T-C is described in ClinVar as Benign. ClinVar VariationId is 1192498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.971 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.-7-39A>G	intron	N/A	NP_001193.2	P12644
BMP4	NM_001347912.1		c.188-92A>G	intron	N/A	NP_001334841.1
BMP4	NM_001347914.2		c.-7-39A>G	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.-7-39A>G	intron	N/A	ENSP00000245451.4	P12644
BMP4	ENST00000558984.1	TSL:1	c.-7-39A>G	intron	N/A	ENSP00000454134.1	P12644
BMP4	ENST00000559087.5	TSL:1	c.-7-39A>G	intron	N/A	ENSP00000453485.1	P12644

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

126945

AN:

151846

Hom.:

55483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.967

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.993

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.978

Gnomad OTH

AF:

0.858

GnomAD2 exomes

AF:

0.887

AC:

215725

AN:

243256

AF XY:

0.894

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.798

Gnomad ASJ exome

AF:

0.963

Gnomad EAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.991

Gnomad NFE exome

AF:

0.977

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.948

AC:

1375728

AN:

1451928

Hom.:

657440

Cov.:

AF XY:

0.946

AC XY:

683594

AN XY:

722946

show subpopulations

African (AFR)

AF:

0.555

AC:

18450

AN:

33226

American (AMR)

AF:

0.798

AC:

35411

AN:

44366

Ashkenazi Jewish (ASJ)

AF:

0.964

AC:

25079

AN:

26008

East Asian (EAS)

AF:

0.760

AC:

30119

AN:

39642

South Asian (SAS)

AF:

0.823

AC:

70374

AN:

85522

European-Finnish (FIN)

AF:

0.991

AC:

50536

AN:

51010

Middle Eastern (MID)

AF:

0.903

AC:

5184

AN:

5744

European-Non Finnish (NFE)

AF:

0.981

AC:

1085488

AN:

1106260

Other (OTH)

AF:

0.916

AC:

55087

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3329

6657

9986

13314

16643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21402

42804

64206

85608

107010

<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:

0.836

AC:

127012

AN:

151964

Hom.:

55507

Cov.:

AF XY:

0.836

AC XY:

62100

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.574

AC:

23729

AN:

41324

American (AMR)

AF:

0.819

AC:

12516

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.967

AC:

3358

AN:

3472

East Asian (EAS)

AF:

0.703

AC:

3599

AN:

5120

South Asian (SAS)

AF:

0.808

AC:

3887

AN:

4812

European-Finnish (FIN)

AF:

0.993

AC:

10546

AN:

10618

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.978

AC:

66489

AN:

68014

Other (OTH)

AF:

0.857

AC:

1808

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

810

1620

2430

3240

4050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.926

Hom.:

48218

Bravo

AF:

0.811

Asia WGS

AF:

0.749

AC:

2604

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Microphthalmia with brain and digit anomalies (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.67

PromoterAI

0.067

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over