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GeneBe

11-27658115-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001709.5(BDNF):c.450G>A(p.Ala150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,614,124 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 5 hom. )

Consequence

BDNF
NM_001709.5 synonymous

Scores

1

Clinical Significance

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

Conservation

PhyloP100: -2.00
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-AS (HGNC:20608): (BDNF antisense RNA)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-27658115-C-T is Benign according to our data. Variant chr11-27658115-C-T is described in ClinVar as [Benign]. Clinvar id is 783114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 517 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.450G>A p.Ala150= synonymous_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.306-126C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.450G>A p.Ala150= synonymous_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.380-126C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00340
AC:
517
AN:
152116
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00335
GnomAD4 exome
AF:
0.000345
AC:
505
AN:
1461890
Hom.:
5
Cov.:
32
AF XY:
0.000289
AC XY:
210
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0123
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00340
AC:
517
AN:
152234
Hom.:
2
Cov.:
32
AF XY:
0.00331
AC XY:
246
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0118
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00128
Hom.:
0
Bravo
AF:
0.00370

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 12, 2018p.Ala150Ala in exon 1J of BDNF: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence and it has been identified in 1.3% (312/24030) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs2353512). ACMG/AMP Criteria applied: BA1; BP4; BP7. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
2.4

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.

Other links and lift over

dbSNP: rs2353512; hg19: chr11-27679662; API