Variant 14-53949881-TC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001202.6(BMP4):c.*150del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00969 in 718,476 control chromosomes in the GnomAD database, including 91 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.014 ( 48 hom., cov: 30)

Exomes 𝑓: 0.0089 ( 43 hom. )

Consequence

BMP4
NM_001202.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:9

Conservation

PhyloP100: -0.138

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP4	NM_001202.6 linkuse as main transcript	c.*150del		3_prime_UTR_variant	4/4	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
BMP4	ENST00000245451.9 linkuse as main transcript	c.*150del	3_prime_UTR_variant	4/4	1	NM_001202.6	ENSP00000245451	P1
BMP4	ENST00000558984.1 linkuse as main transcript	c.*150del	3_prime_UTR_variant	3/3	1		ENSP00000454134	P1
BMP4	ENST00000559087.5 linkuse as main transcript	c.*150del	3_prime_UTR_variant	4/4	1		ENSP00000453485	P1
BMP4	ENST00000417573.5 linkuse as main transcript	c.*150del	3_prime_UTR_variant	4/4	5		ENSP00000394165	P1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

1606

AN:

113536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0111

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.00570

Gnomad MID

AF:

0.0148

Gnomad NFE

AF:

0.00599

Gnomad OTH

AF:

0.0137

GnomAD4 exome

AF:

0.00887

AC:

5364

AN:

604870

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

3445

AN XY:

306826

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.0190

Gnomad4 ASJ exome

AF:

0.00685

Gnomad4 EAS exome

AF:

0.00573

Gnomad4 SAS exome

AF:

0.0735

Gnomad4 FIN exome

AF:

0.00291

Gnomad4 NFE exome

AF:

0.00287

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0141

AC:

1600

AN:

113606

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

993

AN XY:

55266

show subpopulations

Gnomad4 AFR

AF:

0.00138

Gnomad4 AMR

AF:

0.0386

Gnomad4 ASJ

AF:

0.0111

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.00570

Gnomad4 NFE

AF:

0.00599

Gnomad4 OTH

AF:

0.0149

Alfa

AF:

0.000990

Hom.:

Asia WGS

AF:

0.0570

AC:

197

AN:

3450

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cleft Lip +/- Cleft Palate, Autosomal Dominant

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Syndromic Microphthalmia, Dominant

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Orofacial cleft

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

BMP4-Related Syndromic Microphthalmia

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over