Variant 14-53949883-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000245451.9(BMP4):c.*148_*149insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.016 ( 19 hom., cov: 0)

Exomes 𝑓: 0.12 ( 387 hom. )

Consequence

BMP4
ENST00000245451.9 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: -4.04

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

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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.148_149insT		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.148_149insT	3_prime_UTR_variant	4/4	1	NM_001202.6	ENSP00000245451	P1
BMP4	ENST00000558984.1 linkuse as main transcript	c.148_149insT	3_prime_UTR_variant	3/3	1		ENSP00000454134	P1
BMP4	ENST00000559087.5 linkuse as main transcript	c.148_149insT	3_prime_UTR_variant	4/4	1		ENSP00000453485	P1
BMP4	ENST00000417573.5 linkuse as main transcript	c.148_149insT	3_prime_UTR_variant	4/4	5		ENSP00000394165	P1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2088

AN:

134334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0320

Gnomad AMI

AF:

0.0152

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00367

Gnomad EAS

AF:

0.00243

Gnomad SAS

AF:

0.00281

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.0110

Gnomad NFE

AF:

0.00955

Gnomad OTH

AF:

0.0106

GnomAD4 exome

AF:

0.115

AC:

58117

AN:

503284

Hom.:

387

Cov.:

AF XY:

0.114

AC XY:

29098

AN XY:

254452

show subpopulations

Gnomad4 AFR exome

AF:

0.0529

Gnomad4 AMR exome

AF:

0.0697

Gnomad4 ASJ exome

AF:

0.0985

Gnomad4 EAS exome

AF:

0.0316

Gnomad4 SAS exome

AF:

0.0748

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0155

AC:

2088

AN:

134332

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1036

AN XY:

64668

show subpopulations

Gnomad4 AFR

AF:

0.0320

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00367

Gnomad4 EAS

AF:

0.00244

Gnomad4 SAS

AF:

0.00255

Gnomad4 FIN

AF:

0.0204

Gnomad4 NFE

AF:

0.00955

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.00404

Hom.:

747

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Cleft Lip +/- Cleft Palate, Autosomal Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Syndromic Microphthalmia, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Orofacial cleft

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

BMP4-Related Syndromic Microphthalmia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

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