11-27659197-A-T

Position:

• chr11-27659197-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170735.6(BDNF):​c.-633T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 996,850 control chromosomes in the GnomAD database, including 98,075 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11403 hom., cov: 31)
  • Exomes 𝑓: 0.45 (86672 hom.)
• Consequence: BDNF NM_170735.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-612T>A		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-612T>A		intron_variant		1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-612T>A		intron_variant		1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54900 AN: 151888 Hom.: 11404 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.449 AC: 379482 AN: 844846 Hom.: 86672 Cov.: 29 AF XY: 0.450 AC XY: 175698 AN XY: 390442

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.361 AC: 54898 AN: 152004 Hom.: 11403 Cov.: 31 AF XY: 0.360 AC XY: 26782 AN XY: 74292

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.386

Alfa AF: 0.420 Hom.: 1824

Bravo AF: 0.339

Asia WGS AF: 0.292 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.7
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs11030101; hg19: chr11-27680744;