rs12291186

Positions:

• chr11-27674771-A-C

Variant summary

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

The NM_001709.5(BDNF):​c.-21-16186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 971,192 control chromosomes in the GnomAD database, including 3,416 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 0.11 (2502 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (914 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001709.5	c.-21-16186T>G		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.586-806A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-16186T>G		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.660-2211A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17332 AN: 152044 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.0944

GnomAD4 exome AF: 0.00936 AC: 7669 AN: 819030 Hom.: 914 Cov.: 29 AF XY: 0.00843 AC XY: 3192 AN XY: 378656

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.0281

GnomAD4 genome AF: 0.114 AC: 17362 AN: 152162 Hom.: 2502 Cov.: 32 AF XY: 0.116 AC XY: 8601 AN XY: 74418

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00254

Gnomad4 OTH AF: 0.0935

Alfa AF: 0.0409 Hom.: 293

Bravo AF: 0.142

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12291186; hg19: chr11-27696318;