Genetic Variant BDNF:c.-21-1724G>A (chr11-27660309-C-T) – 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.-21-1724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 983,374 control chromosomes in the GnomAD database, including 293 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 0.030 ( 162 hom., cov: 32)

Exomes 𝑓: 0.011 ( 131 hom. )

Consequence

BDNF
NM_001709.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

3 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-21-1724G>A		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.-21-1724G>A		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.-21-1724G>A		intron_variant	Intron 1 of 1	1		ENSP00000432727.1		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4550

AN:

152198

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0788

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.0321

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0154

AC:

1687

AN:

109512

AF XY:

0.0147

show subpopulations

Gnomad AFR exome

AF:

0.0851

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00865

Gnomad EAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.00596

Gnomad NFE exome

AF:

0.00863

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0109

AC:

9036

AN:

831058

Hom.:

131

Cov.:

AF XY:

0.0110

AC XY:

4585

AN XY:

418532

show subpopulations

African (AFR)

AF:

0.0857

AC:

1518

AN:

17714

American (AMR)

AF:

0.0117

AC:

269

AN:

22926

Ashkenazi Jewish (ASJ)

AF:

0.00924

AC:

126

AN:

13630

East Asian (EAS)

AF:

0.0315

AC:

325

AN:

10312

South Asian (SAS)

AF:

0.0148

AC:

949

AN:

64168

European-Finnish (FIN)

AF:

0.00563

AC:

AN:

12266

Middle Eastern (MID)

AF:

0.0579

AC:

218

AN:

3764

European-Non Finnish (NFE)

AF:

0.00763

AC:

4996

AN:

654896

Other (OTH)

AF:

0.0180

AC:

566

AN:

31382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

413

825

1238

1650

2063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0300

AC:

4574

AN:

152316

Hom.:

162

Cov.:

AF XY:

0.0293

AC XY:

2184

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0793

AC:

3296

AN:

41566

American (AMR)

AF:

0.0195

AC:

299

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3468

East Asian (EAS)

AF:

0.0314

AC:

163

AN:

5188

South Asian (SAS)

AF:

0.0122

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00471

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00850

AC:

578

AN:

68020

Other (OTH)

AF:

0.0289

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

229

457

686

914

1143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0172

Hom.:

Bravo

AF:

0.0334

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.77

(source)

DANN

Benign

0.37

PhyloP100

-1.2

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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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