rs56820186

Positions:

• chr11-27657465-T-G

Variant summary

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

The NM_001709.5(BDNF):​c.*356A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 936,852 control chromosomes in the GnomAD database, including 274 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 0.13 (169 hom., cov: 0)
  • Exomes 𝑓: 0.010 (105 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001709.5	c.*356A>C		3_prime_UTR_variant	2/2	ENST00000356660.9
BDNF-AS	NR_033312.1	n.306-776T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.*356A>C		3_prime_UTR_variant	2/2	1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.380-776T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.134 AC: 4625 AN: 34456 Hom.: 161 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.0102 AC: 9214 AN: 902298 Hom.: 105 Cov.: 32 AF XY: 0.0102 AC XY: 4310 AN XY: 421456

Gnomad4 AFR exome AF: 0.0906

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.00945

Gnomad4 EAS exome AF: 0.0293

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.00486

Gnomad4 NFE exome AF: 0.00784

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.135 AC: 4653 AN: 34554 Hom.: 169 Cov.: 0 AF XY: 0.132 AC XY: 2217 AN XY: 16810

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0270 Hom.: 14

Bravo AF: 0.0340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.57

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: rs56820186; hg19: chr11-27679012;