14-53950004-T-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001202.6(BMP4):c.*28A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,613,230 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
BMP4
NM_001202.6 3_prime_UTR
NM_001202.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0760
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 14-53950004-T-A is Benign according to our data. Variant chr14-53950004-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 881588.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00199 (302/151812) while in subpopulation AFR AF= 0.00708 (293/41372). AF 95% confidence interval is 0.00642. There are 2 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 302 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP4 | NM_001202.6 | c.*28A>T | 3_prime_UTR_variant | 4/4 | ENST00000245451.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP4 | ENST00000245451.9 | c.*28A>T | 3_prime_UTR_variant | 4/4 | 1 | NM_001202.6 | P1 | ||
BMP4 | ENST00000558984.1 | c.*28A>T | 3_prime_UTR_variant | 3/3 | 1 | P1 | |||
BMP4 | ENST00000559087.5 | c.*28A>T | 3_prime_UTR_variant | 4/4 | 1 | P1 | |||
BMP4 | ENST00000417573.5 | c.*28A>T | 3_prime_UTR_variant | 4/4 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00199 AC: 302AN: 151694Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000498 AC: 125AN: 250792Hom.: 2 AF XY: 0.000413 AC XY: 56AN XY: 135550
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GnomAD4 exome AF: 0.000193 AC: 282AN: 1461418Hom.: 1 Cov.: 32 AF XY: 0.000171 AC XY: 124AN XY: 727016
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Microphthalmia with brain and digit anomalies Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Orofacial cleft 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at