rs1048220
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001709.5(BDNF):c.374G>T(p.Arg125Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: not found (cov: 32)
Consequence
BDNF
NM_001709.5 missense
NM_001709.5 missense
Scores
8
7
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.00
Genes affected
BDNF (HGNC:1033): (brain derived neurotrophic factor) This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.374G>T | p.Arg125Met | missense_variant | 2/2 | ENST00000356660.9 | |
BDNF-AS | NR_033312.1 | n.306-50C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BDNF | ENST00000356660.9 | c.374G>T | p.Arg125Met | missense_variant | 2/2 | 1 | NM_001709.5 | P4 | |
BDNF-AS | ENST00000651238.1 | n.380-50C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
DEOGEN2
Pathogenic
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;L;L;L;L;L;L;.;L;L;L;L;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);.;Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);.;Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);Loss of MoRF binding (P = 0.0228);.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at