chr4-95123890-T-C
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_001203.3(BMPR1B):c.430T>C(p.Leu144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,610,654 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )
Consequence
BMPR1B
NM_001203.3 synonymous
NM_001203.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.433
Genes affected
BMPR1B (HGNC:1077): (bone morphogenetic protein receptor type 1B) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 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. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 4-95123890-T-C is Benign according to our data. Variant chr4-95123890-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 464044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.433 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000302 (46/152262) while in subpopulation AMR AF= 0.000589 (9/15290). AF 95% confidence interval is 0.000307. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1B | NM_001203.3 | c.430T>C | p.Leu144= | synonymous_variant | 7/13 | ENST00000515059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1B | ENST00000515059.6 | c.430T>C | p.Leu144= | synonymous_variant | 7/13 | 1 | NM_001203.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 250756Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135570
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GnomAD4 exome AF: 0.000298 AC: 435AN: 1458392Hom.: 1 Cov.: 30 AF XY: 0.000336 AC XY: 244AN XY: 725608
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
BMPR1B-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 20, 2023 | 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). - |
Type A2 brachydactyly;C4225404:Acromesomelic dysplasia 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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