11-27658369-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001709.5(BDNF):c.196G>A(p.Val66Met) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,614,068 control chromosomes in the GnomAD database, including 31,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2519 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28821 hom. )

Consequence

BDNF
NM_001709.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 4.94

Publications

4138 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017960966).

BP6

Variant 11-27658369-C-T is Benign according to our data. Variant chr11-27658369-C-T is described in ClinVar as Benign. ClinVar VariationId is 17697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 2	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23190

AN:

152064

Hom.:

2519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.195

AC:

48968

AN:

251276

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.0333

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.190

AC:

277361

AN:

1461886

Hom.:

28821

Cov.:

AF XY:

0.191

AC XY:

138787

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0300

AC:

1006

AN:

33480

American (AMR)

AF:

0.148

AC:

6609

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5700

AN:

26136

East Asian (EAS)

AF:

0.443

AC:

17601

AN:

39700

South Asian (SAS)

AF:

0.192

AC:

16604

AN:

86258

European-Finnish (FIN)

AF:

0.153

AC:

8189

AN:

53418

Middle Eastern (MID)

AF:

0.151

AC:

869

AN:

5768

European-Non Finnish (NFE)

AF:

0.188

AC:

209458

AN:

1112006

Other (OTH)

AF:

0.188

AC:

11325

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17105

34210

51315

68420

85525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7436

14872

22308

29744

37180

<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:

0.152

AC:

23187

AN:

152182

Hom.:

2519

Cov.:

AF XY:

0.154

AC XY:

11438

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0372

AC:

1544

AN:

41542

American (AMR)

AF:

0.159

AC:

2434

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

772

AN:

3470

East Asian (EAS)

AF:

0.473

AC:

2442

AN:

5160

South Asian (SAS)

AF:

0.201

AC:

973

AN:

4832

European-Finnish (FIN)

AF:

0.151

AC:

1596

AN:

10582

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.187

AC:

12717

AN:

67990

Other (OTH)

AF:

0.170

AC:

359

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

967

1933

2900

3866

4833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.183

Hom.:

14165

Bravo

AF:

0.151

TwinsUK

AF:

0.193

AC:

715

ALSPAC

AF:

0.180

AC:

693

ESP6500AA

AF:

0.0418

AC:

184

ESP6500EA

AF:

0.191

AC:

1640

ExAC

AF:

0.194

AC:

23513

Asia WGS

AF:

0.278

AC:

967

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 18, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Benign with respect to pulmonary disease based on high population frequency, Th is variant has been proposed to be associated with a rnage of psychiatric manife stations though the data is not solid and more recent meta-analyses argue agains t a risk effect. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Memory impairment, susceptibility to

Other:1

Apr 03, 2025

OMIM

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.

PhyloP100

4.9

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.72

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;D;D;D;D;D;D;D;D;P;D;D;D;D;D;D;D

Vest4

0.074

MPC

1.6

ClinPred

0.026

GERP RS

5.3

Varity_R

0.22

gMVP

0.66

Mutation Taster

=86/14

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over