11-27658342-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001709.5(BDNF):c.223C>G(p.Gln75Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000208 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q75H) has been classified as Likely benign.
Frequency
Consequence
NM_001709.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.223C>G | p.Gln75Glu | missense_variant | Exon 2 of 2 | ENST00000356660.9 | NP_001700.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251214Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135816
GnomAD4 exome AF: 0.000218 AC: 318AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.000209 AC XY: 152AN XY: 727246
GnomAD4 genome AF: 0.000118 AC: 18AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74302
ClinVar
Submissions by phenotype
BDNF-related disorder Uncertain:1
The BDNF c.469C>G variant is predicted to result in the amino acid substitution p.Gln157Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Inborn genetic diseases Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at