11-27658369-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001709.5(BDNF):c.196G>A(p.Val66Met) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,614,068 control chromosomes in the GnomAD database, including 31,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.15 ( 2519 hom., cov: 32)
Exomes 𝑓: 0.19 ( 28821 hom. )
Consequence
BDNF
NM_001709.5 missense
NM_001709.5 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 4.94
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0017960966).
BP6
?
Variant 11-27658369-C-T is Benign according to our data. Variant chr11-27658369-C-T is described in ClinVar as [Benign]. Clinvar id is 17697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.196G>A | p.Val66Met | missense_variant | 2/2 | ENST00000356660.9 | |
BDNF-AS | NR_033312.1 | n.434C>T | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BDNF | ENST00000356660.9 | c.196G>A | p.Val66Met | missense_variant | 2/2 | 1 | NM_001709.5 | P4 | |
BDNF-AS | ENST00000651238.1 | n.508C>T | non_coding_transcript_exon_variant | 5/8 |
Frequencies
GnomAD3 genomes ? AF: 0.153 AC: 23190AN: 152064Hom.: 2519 Cov.: 32
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GnomAD3 exomes AF: 0.195 AC: 48968AN: 251276Hom.: 6030 AF XY: 0.199 AC XY: 26958AN XY: 135806
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GnomAD4 exome AF: 0.190 AC: 277361AN: 1461886Hom.: 28821 Cov.: 36 AF XY: 0.191 AC XY: 138787AN XY: 727244
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GnomAD4 genome ? AF: 0.152 AC: 23187AN: 152182Hom.: 2519 Cov.: 32 AF XY: 0.154 AC XY: 11438AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 18, 2013 | Benign with respect to pulmonary disease based on high population frequency, Th is variant has been proposed to be associated with a rnage of psychiatric manife stations though the data is not solid and more recent meta-analyses argue agains t a risk effect. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Memory impairment, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Dec 13, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.
MutationTaster
Benign
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
D;D;D;D;D;D;D;D;D;P;D;D;D;D;D;D;D
Vest4
MPC
1.6
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