1-39511860-G-A

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

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410
Variant links:
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]

Genome browser will be placed here

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
BMP8ANM_181809.4 linkuse as main transcriptc.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
BMP8AENST00000331593.6 linkuse as main transcriptc.629G>A p.Arg210His missense_variant 3/71 NM_181809.4 ENSP00000327440 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
37
AN:
121762
Hom.:
0
Cov.:
15
FAILED QC
Gnomad AFR
AF:
0.00100
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000900
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000352
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000283
AC:
35
AN:
1237618
Hom.:
0
Cov.:
18
AF XY:
0.0000161
AC XY:
10
AN XY:
622130
show subpopulations
Gnomad4 AFR exome
AF:
0.000854
Gnomad4 AMR exome
AF:
0.0000251
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000266
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000326
Gnomad4 OTH exome
AF:
0.0000761
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000304
AC:
37
AN:
121906
Hom.:
0
Cov.:
15
AF XY:
0.000291
AC XY:
17
AN XY:
58324
show subpopulations
Gnomad4 AFR
AF:
0.000996
Gnomad4 AMR
AF:
0.0000897
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000352
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000337
Hom.:
0
ExAC
AF:
0.0000445
AC:
5

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 submitterclinical testingAmbry GeneticsMar 17, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.33
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.57
N
REVEL
Benign
0.041
Sift
Benign
0.12
T
Sift4G
Benign
0.090
T
Polyphen
0.026
B
Vest4
0.056
MutPred
0.47
Loss of stability (P = 0.0334);
MVP
0.45
MPC
1.8
ClinPred
0.016
T
GERP RS
1.2
Varity_R
0.028
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770615938; hg19: chr1-39977532; API