chr10-86900031-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004329.3(BMPR1A):c.435G>A(p.Pro145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00762 in 1,614,050 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P145P) has been classified as Likely benign.
Frequency
Consequence
NM_004329.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1A | NM_004329.3 | c.435G>A | p.Pro145= | synonymous_variant | 7/13 | ENST00000372037.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1A | ENST00000372037.8 | c.435G>A | p.Pro145= | synonymous_variant | 7/13 | 1 | NM_004329.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0394 AC: 6001AN: 152132Hom.: 406 Cov.: 32
GnomAD3 exomes AF: 0.0107 AC: 2680AN: 251326Hom.: 160 AF XY: 0.00788 AC XY: 1070AN XY: 135868
GnomAD4 exome AF: 0.00428 AC: 6259AN: 1461800Hom.: 386 Cov.: 32 AF XY: 0.00368 AC XY: 2677AN XY: 727208
GnomAD4 genome AF: 0.0396 AC: 6032AN: 152250Hom.: 412 Cov.: 32 AF XY: 0.0375 AC XY: 2795AN XY: 74460
ClinVar
Submissions by phenotype
not specified Benign:9
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 08, 2020 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 28, 2018 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 28, 2016 | - - |
Hereditary cancer-predisposing syndrome Benign:4
Likely benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Jan 12, 2018 | - - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 22, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 09, 2016 | - - |
Juvenile polyposis syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Polyposis syndrome, hereditary mixed, 2 Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The BMPR1A p.Pro145= variant was identified in dbSNP (ID: rs11818239) as “With Benign, Likely benign allele”, ClinVar (classified benign by Ambry Genetics, Illumina, Invitae, Quest Diagnostics Nichols Institute San Juan Capistrano, ARUP, Color, Prevention Genetics and Mayo Clinic; and likely benign by True Health Diagnostics). The variant was identified in control databases in 3757 (239 homozygous) of 277074 chromosomes at a frequency of 0.01 (Genome Aggregation Database Feb 27, 2017, observed in the following populations: African in 3359 (236 homozygous) of 24018 chromosomes (freq: 0.1), Other in 46 of 6458 chromosomes (freq: 0.007), Latino in 269 (2 homozygous) of 34418 chromosomes (freq: 0.008), European Non-Finnish in 74 (1 homozygous) of 126644 chromosomes (freq: 0.0006), East Asian in 1 of 18866 chromosomes (freq: 0.00005), and South Asian in 8 of 30782 chromosomes (freq: 0.0003), while not observed in the Ashkenazi Jewish and European Finnish populations. The p.Pro145= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence, 5 bases into exon 7, and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Generalized juvenile polyposis/juvenile polyposis coli 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at