6-7727038-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001718.6(BMP6):​c.83G>T​(p.Arg28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 148,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000051 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BMP6
NM_001718.6 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0780
Variant links:
Genes affected
BMP6 (HGNC:1073): (bone morphogenetic protein 6) 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 regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07127854).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BMP6NM_001718.6 linkc.83G>T p.Arg28Leu missense_variant Exon 1 of 7 ENST00000283147.7 NP_001709.1 P22004Q4VBA3B4DUF7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BMP6ENST00000283147.7 linkc.83G>T p.Arg28Leu missense_variant Exon 1 of 7 1 NM_001718.6 ENSP00000283147.6 P22004

Frequencies

GnomAD3 genomes
AF:
0.0000134
AC:
2
AN:
148818
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000667
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:
0.0000150
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000507
AC:
5
AN:
986154
Hom.:
0
Cov.:
30
AF XY:
0.00000646
AC XY:
3
AN XY:
464454
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000348
Gnomad4 OTH exome
AF:
0.0000543
GnomAD4 genome
AF:
0.0000134
AC:
2
AN:
148926
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
72618
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000667
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000150
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
14
DANN
Benign
0.82
DEOGEN2
Benign
0.22
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.31
N
REVEL
Benign
0.047
Sift
Benign
0.78
T
Sift4G
Benign
0.22
T
Polyphen
0.0
B
Vest4
0.25
MutPred
0.27
Gain of catalytic residue at R28 (P = 0.0138);
MVP
0.41
MPC
0.20
ClinPred
0.065
T
GERP RS
-1.7
Varity_R
0.044
gMVP
0.37

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: rs111588693; hg19: chr6-7727271; API