Variant 14-53949883-C-CAT 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.*148_*149insAT 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 0.41 ( 12430 hom., cov: 0)

Exomes 𝑓: 0.30 ( 5314 hom. )

Consequence

BMP4
NM_001202.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:8B: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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 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_149insAT		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_149insAT	3_prime_UTR_variant	4/4	1	NM_001202.6	ENSP00000245451	P1
BMP4	ENST00000558984.1 linkuse as main transcript	c.148_149insAT	3_prime_UTR_variant	3/3	1		ENSP00000454134	P1
BMP4	ENST00000559087.5 linkuse as main transcript	c.148_149insAT	3_prime_UTR_variant	4/4	1		ENSP00000453485	P1
BMP4	ENST00000417573.5 linkuse as main transcript	c.148_149insAT	3_prime_UTR_variant	4/4	5		ENSP00000394165	P1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

55100

AN:

134366

Hom.:

12435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.390

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.393

GnomAD4 exome

AF:

0.301

AC:

148551

AN:

493386

Hom.:

5314

Cov.:

AF XY:

0.301

AC XY:

74973

AN XY:

249276

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.410

AC:

55082

AN:

134360

Hom.:

12430

Cov.:

AF XY:

0.409

AC XY:

26416

AN XY:

64664

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.390

Alfa

AF:

0.305

Hom.:

747

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:8Benign:1

Revision: criteria provided, conflicting classifications

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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