rs12267107
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004329.3(BMPR1A):c.675+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,613,626 control chromosomes in the GnomAD database, including 759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.039 ( 389 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 370 hom. )
Consequence
BMPR1A
NM_004329.3 intron
NM_004329.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.55
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 10-86912396-G-A is Benign according to our data. Variant chr10-86912396-G-A is described in ClinVar as [Benign]. Clinvar id is 259287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86912396-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1A | NM_004329.3 | c.675+12G>A | intron_variant | ENST00000372037.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1A | ENST00000372037.8 | c.675+12G>A | intron_variant | 1 | NM_004329.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0384 AC: 5841AN: 152020Hom.: 385 Cov.: 32
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GnomAD3 exomes AF: 0.0104 AC: 2625AN: 251248Hom.: 151 AF XY: 0.00774 AC XY: 1051AN XY: 135808
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GnomAD4 exome AF: 0.00424 AC: 6203AN: 1461488Hom.: 370 Cov.: 31 AF XY: 0.00365 AC XY: 2657AN XY: 727066
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GnomAD4 genome ? AF: 0.0386 AC: 5868AN: 152138Hom.: 389 Cov.: 32 AF XY: 0.0365 AC XY: 2717AN XY: 74380
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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, 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, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
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 c.675+12G>A variant was identified in dbSNP (ID: rs12267107) as “With Benign allele” and ClinVar (classified as benign by Prevention Genetics, Illumina, Color and Mayo Clinic). The variant was identified in control databases in 3676 (228 homozygous) of 276986 chromosomes at a frequency of 0.01 (Genome Aggregation Database Feb 27, 2017), observed in the following populations: African in 3277 (225 homozygous) of 24004 chromosomes (freq: 0.1), Other in 47 of 6448 chromosomes (freq: 0.007), Latino in 262 (2 homozygous) of 34398 chromosomes (freq: 0.008), European in 81 (1 homozygous) of 126552 chromosomes (freq: 0.0006), and South Asian in 9 of 30778 chromosomes (freq: 0.0003), while it was not observed in the Ashkenazi Jewish, East Asian, or Finnish populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 09, 2016 | - - |
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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at