Variant chr11-27699390-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170734.4(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. 11/13 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
NM_170734.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.310

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 made for transcript

Verdict is Benign. Variant got -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 id is 162789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-27699390-C-T is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-22+774G>A		intron_variant	Intron 1 of 1	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.-22+774G>A		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.-22+93G>A		intron_variant	Intron 1 of 1	1		ENSP00000432727.1		P23560-1

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

GnomAD3 exomes

AF:

0.0355

AC:

8852

AN:

249568

Hom.:

200

AF XY:

0.0357

AC XY:

4838

AN XY:

135404

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 SAS exome

AF:

0.0161

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

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.0288

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.0304

Gnomad4 NFE exome

AF:

0.0577

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0345

AC:

5259

AN:

152262

Hom.:

130

Cov.:

AF XY:

0.0321

AC XY:

2391

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0179

Gnomad4 FIN

AF:

0.0264

Gnomad4 NFE

AF:

0.0543

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0490

Hom.:

357

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.9

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

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over