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GeneBe

11-27658332-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM2_SupportingBP4_Strong

The NM_001709.5(BDNF):c.233G>A(p.Arg78Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152110 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BDNF
NM_001709.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.721

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000657 (1/152110) while in subpopulation NFE AF= 0.0000147 (1/68002). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.067813784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.233G>A p.Arg78Gln missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.397C>T non_coding_transcript_exon_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.233G>A p.Arg78Gln missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.471C>T non_coding_transcript_exon_variant 5/8

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251118
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461888
Hom.:
0
AF XY:
0.00000688
AC XY:
5
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000331
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2021The c.233G>A (p.R78Q) alteration is located in exon 1 (coding exon 1) of the BDNF gene. This alteration results from a G to A substitution at nucleotide position 233, causing the arginine (R) at amino acid position 78 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
Cadd
Benign
22
Dann
Benign
0.96
DEOGEN2
Benign
0.30
T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.027
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.068
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.060
N;N;.;N;N;N;N;N;N;.;N;N;N;N;N;N;.
MutationTaster
Benign
0.99
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.24
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.047
Sift
Benign
0.89
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.65
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.052
B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B
Vest4
0.030
MutPred
0.29
Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);.;Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);.;Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);Gain of methylation at K76 (P = 0.0544);.;
MVP
0.48
MPC
0.73
ClinPred
0.14
T
GERP RS
4.1
Varity_R
0.030
gMVP
0.22

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: rs199638553; hg19: chr11-27679879; API