dbSNP rs12291186: BDNF:c.-21-16186T>G (chr11-27674771-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001709.5(BDNF):c.-21-16186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 971,192 control chromosomes in the GnomAD database, including 3,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 2502 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 914 hom. )

Consequence

BDNF
NM_001709.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

9 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-21-16186T>G		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2	P23560-1A0A0E3SU01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9 link	c.-21-16186T>G		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.-21-16186T>G		intron_variant	Intron 1 of 1	1		ENSP00000432727.1		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17332

AN:

152044

Hom.:

2494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.0944

GnomAD4 exome

AF:

0.00936

AC:

7669

AN:

819030

Hom.:

914

Cov.:

AF XY:

0.00843

AC XY:

3192

AN XY:

378656

show subpopulations

African (AFR)

AF:

0.315

AC:

4818

AN:

15294

American (AMR)

AF:

0.271

AC:

258

AN:

952

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

5080

East Asian (EAS)

AF:

0.184

AC:

649

AN:

3536

South Asian (SAS)

AF:

0.0118

AC:

190

AN:

16168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

272

Middle Eastern (MID)

AF:

0.0175

AC:

AN:

1600

European-Non Finnish (NFE)

AF:

0.00129

AC:

965

AN:

749292

Other (OTH)

AF:

0.0281

AC:

753

AN:

26836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

301

602

903

1204

1505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.114

AC:

17362

AN:

152162

Hom.:

2502

Cov.:

AF XY:

0.116

AC XY:

8601

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.305

AC:

12634

AN:

41486

American (AMR)

AF:

0.224

AC:

3422

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.165

AC:

852

AN:

5174

South Asian (SAS)

AF:

0.0147

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00254

AC:

173

AN:

68014

Other (OTH)

AF:

0.0935

AC:

197

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

633

1266

1899

2532

3165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0375

Hom.:

309

Bravo

AF:

0.142

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.3

(source)

DANN

Benign

0.63

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs12291186

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over