Genetic Variant BDNF:c.-77C>A (chr11-27700731-G-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_001143812.2(BDNF):c.-77C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,184,476 control chromosomes in the GnomAD database, including 34,479 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 ( 3080 hom., cov: 32)

Exomes 𝑓: 0.24 ( 31399 hom. )

Consequence

BDNF
NM_001143812.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

24 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143812.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
BDNF	NM_001143812.2	c.-77C>A	5_prime_UTR	Exon 1 of 2	NP_001137284.1	A0A0E3SU01
BDNF	NM_001143810.2	c.-59+240C>A	intron	N/A	NP_001137282.1	P23560-4
BDNF	NM_001143809.2	c.66+240C>A	intron	N/A	NP_001137281.1	P23560-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BDNF	ENST00000530861.5	TSL:1	c.-77C>A	5_prime_UTR	Exon 1 of 2	ENSP00000435564.1	P23560-1
BDNF	ENST00000438929.5	TSL:1	c.-59+240C>A	intron	N/A	ENSP00000414303.1	P23560-4
BDNF	ENST00000314915.6	TSL:1	c.3+20681C>A	intron	N/A	ENSP00000320002.6	P23560-2

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28222

AN:

151988

Hom.:

3080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.0105

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.192

GnomAD4 exome

AF:

0.241

AC:

248674

AN:

1032372

Hom.:

31399

Cov.:

AF XY:

0.236

AC XY:

116606

AN XY:

493910

show subpopulations

African (AFR)

AF:

0.0946

AC:

1980

AN:

20922

American (AMR)

AF:

0.183

AC:

2214

AN:

12102

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

1341

AN:

9576

East Asian (EAS)

AF:

0.00600

AC:

AN:

11998

South Asian (SAS)

AF:

0.113

AC:

6553

AN:

57810

European-Finnish (FIN)

AF:

0.252

AC:

2309

AN:

9168

Middle Eastern (MID)

AF:

0.125

AC:

286

AN:

2284

European-Non Finnish (NFE)

AF:

0.260

AC:

226303

AN:

871660

Other (OTH)

AF:

0.207

AC:

7616

AN:

36852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

10250

20500

30751

41001

51251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9096

18192

27288

36384

45480

<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:

28227

AN:

152104

Hom.:

3080

Cov.:

AF XY:

0.181

AC XY:

13430

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.103

AC:

4278

AN:

41538

American (AMR)

AF:

0.189

AC:

2898

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3466

East Asian (EAS)

AF:

0.0105

AC:

AN:

5144

South Asian (SAS)

AF:

0.108

AC:

523

AN:

4822

European-Finnish (FIN)

AF:

0.249

AC:

2643

AN:

10594

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16787

AN:

67938

Other (OTH)

AF:

0.193

AC:

406

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1125

2250

3376

4501

5626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.143

Hom.:

337

Bravo

AF:

0.181

Asia WGS

AF:

0.0960

AC:

333

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.6

(source)

DANN

Benign

0.84

PhyloP100

0.0070

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=296/4

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