Genetic Variant NM_001709.5:c.-46C>T (chr11-27700188-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001709.5(BDNF):c.-46C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 985,630 control chromosomes in the GnomAD database, including 2,438 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.061 ( 400 hom., cov: 32)

Exomes 𝑓: 0.063 ( 2038 hom. )

Consequence

BDNF
NM_001709.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.49

Publications

43 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-46C>T		5_prime_UTR_variant	Exon 1 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.-46C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_001709.5	ENSP00000349084.4		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.0609

AC:

9264

AN:

152076

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0467

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0425

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.0976

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0526

GnomAD4 exome

AF:

0.0628

AC:

52326

AN:

833438

Hom.:

2038

Cov.:

AF XY:

0.0637

AC XY:

24503

AN XY:

384956

show subpopulations

African (AFR)

AF:

0.0507

AC:

800

AN:

15792

American (AMR)

AF:

0.0345

AC:

AN:

986

Ashkenazi Jewish (ASJ)

AF:

0.0526

AC:

271

AN:

5154

East Asian (EAS)

AF:

0.0344

AC:

125

AN:

3638

South Asian (SAS)

AF:

0.255

AC:

4200

AN:

16472

European-Finnish (FIN)

AF:

0.0857

AC:

AN:

280

Middle Eastern (MID)

AF:

0.0782

AC:

127

AN:

1624

European-Non Finnish (NFE)

AF:

0.0587

AC:

44702

AN:

762178

Other (OTH)

AF:

0.0748

AC:

2043

AN:

27314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

3172

6344

9516

12688

15860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2416

4832

7248

9664

12080

<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:

0.0611

AC:

9294

AN:

152192

Hom.:

400

Cov.:

AF XY:

0.0664

AC XY:

4943

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0472

AC:

1960

AN:

41542

American (AMR)

AF:

0.0423

AC:

648

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.0428

AC:

220

AN:

5142

South Asian (SAS)

AF:

0.246

AC:

1186

AN:

4822

European-Finnish (FIN)

AF:

0.0976

AC:

1035

AN:

10608

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0574

AC:

3900

AN:

67988

Other (OTH)

AF:

0.0530

AC:

112

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

419

838

1256

1675

2094

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:

0.0593

Hom.:

Bravo

AF:

0.0511

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Variant of unknown significance

Uncertain:1

Jun 15, 2004

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

2.5

PromoterAI

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over