Genetic Variant BMP4:c.*148_*149insAAAAAT (chr14-53949883-C-CATTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001202.6(BMP4):c.*148_*149insAAAAAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000030 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000053 ( 3 hom. )

Consequence

BMP4
NM_001202.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.04

Publications

2 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

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.148_149insAAAAAT	3_prime_UTR	Exon 4 of 4	NP_001193.2	P12644
BMP4	NM_001347912.1		c.148_149insAAAAAT	3_prime_UTR	Exon 4 of 4	NP_001334841.1
BMP4	NM_001347914.2		c.148_149insAAAAAT	3_prime_UTR	Exon 3 of 3	NP_001334843.1	P12644

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP4	ENST00000245451.9	TSL:1 MANE Select	c.148_149insAAAAAT	3_prime_UTR	Exon 4 of 4	ENSP00000245451.4	P12644
BMP4	ENST00000558984.1	TSL:1	c.148_149insAAAAAT	3_prime_UTR	Exon 3 of 3	ENSP00000454134.1	P12644
BMP4	ENST00000559087.5	TSL:1	c.148_149insAAAAAT	3_prime_UTR	Exon 4 of 4	ENSP00000453485.1	P12644

Frequencies

GnomAD3 genomes

AF:

0.0000298

AC:

AN:

134408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000463

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000530

AC:

AN:

509904

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

257846

show subpopulations

African (AFR)

AF:

0.000242

AC:

AN:

12420

American (AMR)

AF:

0.0000666

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12400

East Asian (EAS)

AF:

0.00

AC:

AN:

28830

South Asian (SAS)

AF:

0.0000680

AC:

AN:

29396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1930

European-Non Finnish (NFE)

AF:

0.0000502

AC:

AN:

358892

Other (OTH)

AF:

0.000114

AC:

AN:

26222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000298

AC:

AN:

134408

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33616

American (AMR)

AF:

0.00

AC:

AN:

13152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3272

East Asian (EAS)

AF:

0.00

AC:

AN:

4534

South Asian (SAS)

AF:

0.00

AC:

AN:

3556

European-Finnish (FIN)

AF:

0.000118

AC:

AN:

8498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000463

AC:

AN:

64760

Other (OTH)

AF:

0.00

AC:

AN:

1894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-4.0

Splicing

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