rs12291186

Variant names:

• chr11-27674771-A-C
• rs12291186
• NM_001709.5:c.-21-16186T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-21-16186T>G		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-429T>G		intron	N/A	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.67-16186T>G		intron	N/A	NP_001137281.1	P23560-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-16186T>G		intron	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.-58-429T>G		intron	N/A	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.25-16186T>G		intron	N/A	ENSP00000379309.2	P23560-3

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

African (AFR) AF: 0.315 AC: 4818 AN: 15294

American (AMR) AF: 0.271 AC: 258 AN: 952

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 8 AN: 5080

East Asian (EAS) AF: 0.184 AC: 649 AN: 3536

South Asian (SAS) AF: 0.0118 AC: 190 AN: 16168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 272

Middle Eastern (MID) AF: 0.0175 AC: 28 AN: 1600

European-Non Finnish (NFE) AF: 0.00129 AC: 965 AN: 749292

Other (OTH) AF: 0.0281 AC: 753 AN: 26836

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

African (AFR) AF: 0.305 AC: 12634 AN: 41486

American (AMR) AF: 0.224 AC: 3422 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.165 AC: 852 AN: 5174

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68014

Other (OTH) AF: 0.0935 AC: 197 AN: 2108

Alfa AF: 0.0375 Hom.: 309

Bravo AF: 0.142

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12291186; hg19: chr11-27696318;