rs41271330
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_021073.4(BMP5):c.846C>T(p.Asn282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,612,094 control chromosomes in the GnomAD database, including 12,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.093 ( 824 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11862 hom. )
Consequence
BMP5
NM_021073.4 synonymous
NM_021073.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.255
Genes affected
BMP5 (HGNC:1072): (bone morphogenetic protein 5) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]
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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=-0.53).
BP6
Variant 6-55774230-G-A is Benign according to our data. Variant chr6-55774230-G-A is described in ClinVar as [Benign]. Clinvar id is 3060109.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.255 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP5 | NM_021073.4 | c.846C>T | p.Asn282= | synonymous_variant | 4/7 | ENST00000370830.4 | |
BMP5 | NM_001329754.2 | c.846C>T | p.Asn282= | synonymous_variant | 4/6 | ||
BMP5 | NM_001329756.2 | c.846C>T | p.Asn282= | synonymous_variant | 4/5 | ||
BMP5 | XM_011514817.4 | c.846C>T | p.Asn282= | synonymous_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP5 | ENST00000370830.4 | c.846C>T | p.Asn282= | synonymous_variant | 4/7 | 1 | NM_021073.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0933 AC: 14166AN: 151836Hom.: 815 Cov.: 32
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GnomAD3 exomes AF: 0.112 AC: 28047AN: 251020Hom.: 1768 AF XY: 0.109 AC XY: 14734AN XY: 135646
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GnomAD4 exome AF: 0.124 AC: 180330AN: 1460142Hom.: 11862 Cov.: 32 AF XY: 0.120 AC XY: 87421AN XY: 726434
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GnomAD4 genome AF: 0.0934 AC: 14191AN: 151952Hom.: 824 Cov.: 32 AF XY: 0.0919 AC XY: 6823AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
BMP5-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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