rs6265

Positions:

chr11-27658369-C-T

Variant summary

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

The ENST00000356660.9(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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2519 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28821 hom. )

Consequence

BDNF
ENST00000356660.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.94

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
BDNF	NM_001709.5 linkuse as main transcript	c.196G>A	p.Val66Met	missense_variant	2/2	ENST00000356660.9	NP_001700.2
BDNF-AS	NR_033312.1 linkuse as main transcript	n.434C>T		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9 linkuse as main transcript	c.196G>A	p.Val66Met	missense_variant	2/2	1	NM_001709.5	ENSP00000349084	P4	P23560-1
BDNF-AS	ENST00000651238.1 linkuse as main transcript	n.508C>T		non_coding_transcript_exon_variant	5/8

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

GnomAD3 exomes

AF:

0.195

AC:

48968

AN:

251276

Hom.:

6030

AF XY:

0.199

AC XY:

26958

AN XY:

135806

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 SAS exome

AF:

0.194

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

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.152

AC:

23187

AN:

152182

Hom.:

2519

Cov.:

AF XY:

0.154

AC XY:

11438

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0372

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.189

Hom.:

7433

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 18, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Memory impairment, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 13, 2022

- -

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

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;.

MutationTaster

Benign

9.8e-7

P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P

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

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

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