Menu
GeneBe

11-27658437-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_001709.5(BDNF):c.128T>C(p.Leu43Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BDNF
NM_001709.5 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

Links

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1768882).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.128T>C p.Leu43Pro missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.502A>G 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.128T>C p.Leu43Pro missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.576A>G non_coding_transcript_exon_variant 5/8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000159
AC:
1
AN:
628774
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
342528
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000302

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 GeneticsFeb 03, 2022The c.128T>C (p.L43P) alteration is located in exon 1 (coding exon 1) of the BDNF gene. This alteration results from a T to C substitution at nucleotide position 128, causing the leucine (L) at amino acid position 43 to be replaced by a proline (P). 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
0.080
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Benign
-0.21
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.18
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
1.8
L;L;.;L;L;L;L;L;L;.;L;L;L;L;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.040
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.39
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.99
D;D;D;D;D;D;D;D;D;B;D;D;D;D;D;D;D
Vest4
0.21
MutPred
0.45
Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);.;Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);.;Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);Gain of disorder (P = 0.0103);.;
MVP
0.60
MPC
2.1
ClinPred
0.88
D
GERP RS
6.2
Varity_R
0.35
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27679984; API