Variant chr11-27658057-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001709.5(BDNF):c.508G>A(p.Val170Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,894 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 Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

BDNF
NM_001709.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.17

Variant links:

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]

BDNF links:

BDNF-AS (HGNC:20608): (BDNF antisense RNA)

BDNF-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2743793).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	2/2	ENST00000356660.9	NP_001700.2
BDNF-AS	NR_033312.1 linkuse as main transcript	n.306-184C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	2/2	1	NM_001709.5	ENSP00000349084	P4	P23560-1
BDNF-AS	ENST00000651238.1 linkuse as main transcript	n.380-184C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BDNF-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2024

The BDNF c.754G>A variant is predicted to result in the amino acid substitution p.Val252Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.28

T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.27

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.92

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

0.61

PROVEAN

Benign

-0.46

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.34

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.16

B;B;B;B;B;B;B;B;B;D;B;B;B;B;B;B;B

Vest4

0.44

MutPred

0.73

Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);.;Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);.;Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);Loss of methylation at K169 (P = 0.0778);.;

MVP

0.53

MPC

1.2

ClinPred

0.28

GERP RS

6.1

Varity_R

0.75

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over