1-39511860-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_181809.4(BMP8A):c.629G>A(p.Arg210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 15)
Exomes 𝑓: 0.000028 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BMP8A
NM_181809.4 missense
NM_181809.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: -0.0410
Genes affected
BMP8A (HGNC:21650): (bone morphogenetic protein 8a) 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. This protein may play a role in development of the reproductive system. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.025740534).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BMP8A | NM_181809.4 | c.629G>A | p.Arg210His | missense_variant | 3/7 | ENST00000331593.6 | NP_861525.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BMP8A | ENST00000331593.6 | c.629G>A | p.Arg210His | missense_variant | 3/7 | 1 | NM_181809.4 | ENSP00000327440 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 37AN: 121762Hom.: 0 Cov.: 15 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000283 AC: 35AN: 1237618Hom.: 0 Cov.: 18 AF XY: 0.0000161 AC XY: 10AN XY: 622130
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000304 AC: 37AN: 121906Hom.: 0 Cov.: 15 AF XY: 0.000291 AC XY: 17AN XY: 58324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 17, 2023 | The c.629G>A (p.R210H) alteration is located in exon 3 (coding exon 3) of the BMP8A gene. This alteration results from a G to A substitution at nucleotide position 629, causing the arginine (R) at amino acid position 210 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of stability (P = 0.0334);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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