dbSNP rs10835210: BDNF:c.-21-15778G>T (chr11-27674363-C-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001709.5(BDNF):c.-21-15778G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,518,238 control chromosomes in the GnomAD database, including 129,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9923 hom., cov: 32)

Exomes 𝑓: 0.41 ( 119966 hom. )

Consequence

BDNF
NM_001709.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 11-27674363-C-A is Benign according to our data. Variant chr11-27674363-C-A is described in ClinVar as [Benign]. Clinvar id is 1276343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5 link	c.-21-15778G>T		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.-21-15778G>T		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4		P23560-1
BDNF	ENST00000533131.5 link	c.-21-15778G>T		intron_variant	Intron 1 of 1	1		ENSP00000432727.1		P23560-1

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50162

AN:

151908

Hom.:

9924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.345

GnomAD4 exome

AF:

0.412

AC:

563187

AN:

1366212

Hom.:

119966

Cov.:

AF XY:

0.411

AC XY:

275534

AN XY:

670286

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.265

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.330

AC:

50157

AN:

152026

Hom.:

9923

Cov.:

AF XY:

0.331

AC XY:

24559

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.408

Hom.:

13390

Bravo

AF:

0.305

Asia WGS

AF:

0.277

AC:

966

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.73

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