14-53949883-C-CATT

Variant summary

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

The NM_001202.6(BMP4):​c.*148_*149insAAT 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 0.045 ( 149 hom., cov: 0)
Exomes 𝑓: 0.048 ( 249 hom. )

Consequence

BMP4
NM_001202.6 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BMP4NM_001202.6 linkc.*148_*149insAAT 3_prime_UTR_variant Exon 4 of 4 ENST00000245451.9 NP_001193.2 P12644Q53XC5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BMP4ENST00000245451 linkc.*148_*149insAAT 3_prime_UTR_variant Exon 4 of 4 1 NM_001202.6 ENSP00000245451.4 P12644
BMP4ENST00000558984 linkc.*148_*149insAAT 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000454134.1 P12644
BMP4ENST00000559087 linkc.*148_*149insAAT 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000453485.1 P12644
BMP4ENST00000417573 linkc.*148_*149insAAT 3_prime_UTR_variant Exon 4 of 4 5 ENSP00000394165.1 P12644

Frequencies

GnomAD3 genomes
AF:
0.0448
AC:
6022
AN:
134394
Hom.:
147
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0632
Gnomad AMI
AF:
0.0281
Gnomad AMR
AF:
0.0318
Gnomad ASJ
AF:
0.0761
Gnomad EAS
AF:
0.0651
Gnomad SAS
AF:
0.0509
Gnomad FIN
AF:
0.0365
Gnomad MID
AF:
0.0404
Gnomad NFE
AF:
0.0356
Gnomad OTH
AF:
0.0566
GnomAD4 exome
AF:
0.0476
AC:
24032
AN:
505274
Hom.:
249
Cov.:
0
AF XY:
0.0476
AC XY:
12154
AN XY:
255582
show subpopulations
Gnomad4 AFR exome
AF:
0.0463
Gnomad4 AMR exome
AF:
0.0321
Gnomad4 ASJ exome
AF:
0.0672
Gnomad4 EAS exome
AF:
0.0420
Gnomad4 SAS exome
AF:
0.0533
Gnomad4 FIN exome
AF:
0.0484
Gnomad4 NFE exome
AF:
0.0475
Gnomad4 OTH exome
AF:
0.0471
GnomAD4 genome
AF:
0.0448
AC:
6027
AN:
134388
Hom.:
149
Cov.:
0
AF XY:
0.0442
AC XY:
2861
AN XY:
64688
show subpopulations
Gnomad4 AFR
AF:
0.0633
Gnomad4 AMR
AF:
0.0318
Gnomad4 ASJ
AF:
0.0761
Gnomad4 EAS
AF:
0.0647
Gnomad4 SAS
AF:
0.0507
Gnomad4 FIN
AF:
0.0365
Gnomad4 NFE
AF:
0.0356
Gnomad4 OTH
AF:
0.0596
Alfa
AF:
0.0192
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
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Syndromic Microphthalmia, Dominant Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Orofacial cleft Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

BMP4-Related Syndromic Microphthalmia Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:1
Aug 15, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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.

Other links and lift over

dbSNP: rs796563569; hg19: chr14-54416601; API