ENST00000530786.5:n.*1229A>C – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000530786.5(BDNF):n.*1229A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 936,852 control chromosomes in the GnomAD database, including 274 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 0.13 ( 169 hom., cov: 0)

Exomes 𝑓: 0.010 ( 105 hom. )

Consequence

BDNF
ENST00000530786.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.*356A>C		3_prime_UTR_variant	Exon 2 of 2	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.*356A>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.*356A>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000432727.1		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

4625

AN:

34456

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.0753

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.0102

AC:

9214

AN:

902298

Hom.:

105

Cov.:

AF XY:

0.0102

AC XY:

4310

AN XY:

421456

show subpopulations

African (AFR)

AF:

0.0906

AC:

1559

AN:

17214

American (AMR)

AF:

0.0116

AC:

AN:

4848

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

AN:

6880

East Asian (EAS)

AF:

0.0293

AC:

216

AN:

7360

South Asian (SAS)

AF:

0.0148

AC:

386

AN:

26096

European-Finnish (FIN)

AF:

0.00486

AC:

AN:

3500

Middle Eastern (MID)

AF:

0.0448

AC:

AN:

1852

European-Non Finnish (NFE)

AF:

0.00784

AC:

6304

AN:

803728

Other (OTH)

AF:

0.0171

AC:

528

AN:

30820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

491

981

1472

1962

2453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.135

AC:

4653

AN:

34554

Hom.:

169

Cov.:

AF XY:

0.132

AC XY:

2217

AN XY:

16810

show subpopulations

African (AFR)

AF:

0.175

AC:

3356

AN:

19190

American (AMR)

AF:

0.0744

AC:

308

AN:

4138

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

AN:

206

East Asian (EAS)

AF:

0.296

AC:

160

AN:

540

South Asian (SAS)

AF:

0.0825

AC:

AN:

824

European-Finnish (FIN)

AF:

0.0353

AC:

AN:

1390

Middle Eastern (MID)

AF:

0.289

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0753

AC:

581

AN:

7718

Other (OTH)

AF:

0.142

AC:

AN:

430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

219

438

658

877

1096

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:

0.0184

Hom.:

Bravo

AF:

0.0340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

(source)

DANN

Benign

0.57

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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