Genetic Variant NM_001202.6:c.*272A>G (chr14-53949760-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001202.6(BMP4):c.*272A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000366 in 355,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

BMP4
NM_001202.6 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 6.83

Publications

0 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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.*272A>G	3_prime_UTR	Exon 4 of 4	NP_001193.2	P12644
BMP4	NM_001347912.1		c.*272A>G	3_prime_UTR	Exon 4 of 4	NP_001334841.1
BMP4	NM_001347914.2		c.*272A>G	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.*272A>G	3_prime_UTR	Exon 4 of 4	ENSP00000245451.4	P12644
BMP4	ENST00000558984.1	TSL:1	c.*272A>G	3_prime_UTR	Exon 3 of 3	ENSP00000454134.1	P12644
BMP4	ENST00000559087.5	TSL:1	c.*272A>G	3_prime_UTR	Exon 4 of 4	ENSP00000453485.1	P12644

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000443

AC:

AN:

203378

Hom.:

Cov.:

AF XY:

0.0000474

AC XY:

AN XY:

105392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6614

American (AMR)

AF:

0.00

AC:

AN:

7960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7032

East Asian (EAS)

AF:

0.00

AC:

AN:

14966

South Asian (SAS)

AF:

0.00

AC:

AN:

13906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

916

European-Non Finnish (NFE)

AF:

0.0000463

AC:

AN:

129524

Other (OTH)

AF:

0.000242

AC:

AN:

12402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68054

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cleft Lip +/- Cleft Palate, Autosomal Dominant (1)

Orofacial cleft 11 (1)

Syndromic Microphthalmia, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

6.8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over