rs747266339
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_004329.3(BMPR1A):c.510C>T(p.Phe170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,720 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
BMPR1A
NM_004329.3 synonymous
NM_004329.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.35
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 10-86900106-C-T is Benign according to our data. Variant chr10-86900106-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 183788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.35 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1A | NM_004329.3 | c.510C>T | p.Phe170= | synonymous_variant | 7/13 | ENST00000372037.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1A | ENST00000372037.8 | c.510C>T | p.Phe170= | synonymous_variant | 7/13 | 1 | NM_004329.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251158Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135768
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461528Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727090
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 13, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 12, 2021 | - - |
Juvenile polyposis syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Mar 02, 2023 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
BMPR1A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 29, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Generalized juvenile polyposis/juvenile polyposis coli Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 26, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at