Genetic Variant BDNF:c.-21-1464G>C (chr11-27660049-C-G) – 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.-21-1464G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 387,484 control chromosomes in the GnomAD database, including 9,716 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 0.19 ( 3090 hom., cov: 32)

Exomes 𝑓: 0.23 ( 6626 hom. )

Consequence

BDNF
NM_001709.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

33 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=-0.69).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-21-1464G>C		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.-21-1464G>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.-21-1464G>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28281

AN:

152004

Hom.:

3089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.229

AC:

53864

AN:

235362

Hom.:

6626

AF XY:

0.221

AC XY:

26562

AN XY:

120420

show subpopulations

African (AFR)

AF:

0.0985

AC:

367

AN:

3724

American (AMR)

AF:

0.165

AC:

276

AN:

1670

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

461

AN:

3488

East Asian (EAS)

AF:

0.00321

AC:

AN:

2490

South Asian (SAS)

AF:

0.113

AC:

2672

AN:

23576

European-Finnish (FIN)

AF:

0.248

AC:

1688

AN:

6802

Middle Eastern (MID)

AF:

0.122

AC:

285

AN:

2332

European-Non Finnish (NFE)

AF:

0.254

AC:

46001

AN:

181246

Other (OTH)

AF:

0.210

AC:

2106

AN:

10034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1994

3988

5981

7975

9969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<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:

0.186

AC:

28287

AN:

152122

Hom.:

3090

Cov.:

AF XY:

0.181

AC XY:

13446

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.103

AC:

4290

AN:

41532

American (AMR)

AF:

0.186

AC:

2848

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

444

AN:

3468

East Asian (EAS)

AF:

0.0104

AC:

AN:

5180

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4814

European-Finnish (FIN)

AF:

0.252

AC:

2659

AN:

10566

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16867

AN:

67976

Other (OTH)

AF:

0.194

AC:

408

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1160

2320

3480

4640

5800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.207

Hom.:

442

Bravo

AF:

0.182

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.1

PromoterAI

0.012

Neutral

(source)

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