Genetic Variant ENST00000314915.6:c.3+20270G>A (chr11-27701142-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000314915.6(BDNF):c.3+20270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,246,492 control chromosomes in the GnomAD database, including 4,614 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 0.061 ( 404 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4210 hom. )

Consequence

BDNF
ENST00000314915.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96

Publications

15 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:

ENSG00000255496 (HGNC:):

ENSG00000255496 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314915.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
BDNF	NM_170731.5	c.3+20270G>A	intron	N/A	NP_733927.1
BDNF	NM_001143805.1	c.-22+19502G>A	intron	N/A	NP_001137277.1
BDNF	NM_001143806.1	c.-22+19287G>A	intron	N/A	NP_001137278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BDNF	ENST00000314915.6	TSL:1	c.3+20270G>A	intron	N/A	ENSP00000320002.6
BDNF	ENST00000395978.7	TSL:1	c.-22+19287G>A	intron	N/A	ENSP00000379302.3
BDNF	ENST00000395981.7	TSL:1	c.-22+19204G>A	intron	N/A	ENSP00000379305.3

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9284

AN:

152114

Hom.:

400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0467

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.0979

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0575

Gnomad OTH

AF:

0.0531

GnomAD4 exome

AF:

0.0710

AC:

77729

AN:

1094260

Hom.:

4210

Cov.:

AF XY:

0.0779

AC XY:

41724

AN XY:

535882

show subpopulations

African (AFR)

AF:

0.0484

AC:

1124

AN:

23228

American (AMR)

AF:

0.0259

AC:

721

AN:

27790

Ashkenazi Jewish (ASJ)

AF:

0.0505

AC:

780

AN:

15444

East Asian (EAS)

AF:

0.0373

AC:

453

AN:

12150

South Asian (SAS)

AF:

0.245

AC:

18189

AN:

74102

European-Finnish (FIN)

AF:

0.0923

AC:

2449

AN:

26528

Middle Eastern (MID)

AF:

0.0747

AC:

319

AN:

4270

European-Non Finnish (NFE)

AF:

0.0583

AC:

50768

AN:

871316

Other (OTH)

AF:

0.0742

AC:

2926

AN:

39432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

3178

6357

9535

12714

15892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2344

4688

7032

9376

11720

<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:

0.0612

AC:

9314

AN:

152232

Hom.:

404

Cov.:

AF XY:

0.0666

AC XY:

4961

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0472

AC:

1959

AN:

41532

American (AMR)

AF:

0.0424

AC:

649

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.0425

AC:

220

AN:

5180

South Asian (SAS)

AF:

0.246

AC:

1188

AN:

4820

European-Finnish (FIN)

AF:

0.0979

AC:

1038

AN:

10598

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0576

AC:

3914

AN:

68006

Other (OTH)

AF:

0.0535

AC:

113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

423

846

1268

1691

2114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0573

Hom.:

Bravo

AF:

0.0512

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.0

PromoterAI

-0.014

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over