chr10-86892118-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004329.3(BMPR1A):c.231-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,452,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
BMPR1A
NM_004329.3 splice_polypyrimidine_tract, intron
NM_004329.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.001450
2
Clinical Significance
Conservation
PhyloP100: 0.507
Genes affected
BMPR1A (HGNC:1076): (bone morphogenetic protein receptor type 1A) The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 10-86892118-C-A is Benign according to our data. Variant chr10-86892118-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1097654.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1A | NM_004329.3 | c.231-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000372037.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1A | ENST00000372037.8 | c.231-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004329.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000826 AC: 12AN: 1452922Hom.: 0 Cov.: 29 AF XY: 0.00000553 AC XY: 4AN XY: 723458
GnomAD4 exome
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1452922
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29
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4
AN XY:
723458
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GnomAD4 genome ? Cov.: 32
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32
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Juvenile polyposis syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | This variant causes a C to A nucleotide substitution at the -9 position of intron 4 of the BMPR1A gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at