11-27699390-C-T

Variant names:

Variant summary

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

The ENST00000395986.6(BDNF):c.16G>A(p.Glu6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 1,614,100 control chromosomes in the GnomAD database, including 2,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 130 hom., cov: 31)

Exomes 𝑓: 0.049 ( 2042 hom. )

Consequence

BDNF
ENST00000395986.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.310

Publications

18 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:

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=0.0022384524).

BP6

Variant 11-27699390-C-T is Benign according to our data. Variant chr11-27699390-C-T is described in ClinVar as Benign. ClinVar VariationId is 162789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395986.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BDNF	NM_001709.5	MANE Select	c.-22+774G>A		intron	N/A	NP_001700.2
BDNF	NM_170734.4		c.16G>A	p.Glu6Lys	missense	Exon 1 of 2	NP_733930.1
BDNF	NM_001143810.2		c.-59+1581G>A		intron	N/A	NP_001137282.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BDNF	ENST00000395986.6	TSL:1	c.16G>A	p.Glu6Lys	missense	Exon 1 of 2	ENSP00000379309.2
BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-22+774G>A		intron	N/A	ENSP00000349084.4
BDNF	ENST00000438929.5	TSL:1	c.-59+1581G>A		intron	N/A	ENSP00000414303.1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5257

AN:

152144

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0395

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0393

GnomAD2 exomes

AF:

0.0355

AC:

8852

AN:

249568

AF XY:

0.0357

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.0536

Gnomad OTH exome

AF:

0.0472

GnomAD4 exome

AF:

0.0494

AC:

72199

AN:

1461838

Hom.:

2042

Cov.:

AF XY:

0.0482

AC XY:

35070

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00950

AC:

318

AN:

33480

American (AMR)

AF:

0.0288

AC:

1289

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

526

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0175

AC:

1512

AN:

86258

European-Finnish (FIN)

AF:

0.0304

AC:

1625

AN:

53420

Middle Eastern (MID)

AF:

0.0364

AC:

210

AN:

5768

European-Non Finnish (NFE)

AF:

0.0577

AC:

64147

AN:

1111958

Other (OTH)

AF:

0.0425

AC:

2569

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3871

7741

11612

15482

19353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2380

4760

7140

9520

11900

<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:

0.0345

AC:

5259

AN:

152262

Hom.:

130

Cov.:

AF XY:

0.0321

AC XY:

2391

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0106

AC:

441

AN:

41560

American (AMR)

AF:

0.0395

AC:

604

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5160

South Asian (SAS)

AF:

0.0179

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0264

AC:

280

AN:

10618

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0543

AC:

3691

AN:

68022

Other (OTH)

AF:

0.0389

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

252

504

756

1008

1260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0476

Hom.:

712

Bravo

AF:

0.0351

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.0124

AC:

ESP6500EA

AF:

0.0474

AC:

390

ExAC

AF:

0.0357

AC:

4315

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0529

EpiControl

AF:

0.0504

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu6Lys in exon 1I of BDNF: This variant is not expected to have clinical signif icance because it has been identified in 4.7% (390/8232) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs66866077).

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.9

(source)

DANN

Benign

0.88

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

PhyloP100

0.31

PROVEAN

Benign

-0.070

REVEL

Benign

0.048

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.94

Vest4

0.048

ClinPred

0.030

GERP RS

0.20

PromoterAI

-0.015

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over