11-27658118-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001709.5(BDNF):c.447G>A(p.Thr149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
BDNF
NM_001709.5 synonymous
NM_001709.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.15
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 11-27658118-C-T is Benign according to our data. Variant chr11-27658118-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2309743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-27658118-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-3.14 with no splicing effect.
BS2
High AC in GnomAd4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.447G>A | p.Thr149= | synonymous_variant | 2/2 | ENST00000356660.9 | |
BDNF-AS | NR_033312.1 | n.306-123C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BDNF | ENST00000356660.9 | c.447G>A | p.Thr149= | synonymous_variant | 2/2 | 1 | NM_001709.5 | P4 | |
BDNF-AS | ENST00000651238.1 | n.380-123C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000115 AC: 29AN: 251440Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135892
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GnomAD4 exome AF: 0.000183 AC: 268AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 137AN XY: 727248
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74432
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
BDNF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 03, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at