rs1013402

Variant names:

• chr11-27690834-A-G
• rs1013402
• NM_001709.5:c.-22+9330T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001709.5(BDNF):​c.-22+9330T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,978 control chromosomes in the GnomAD database, including 5,133 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 0.24 (5133 hom., cov: 31)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 19 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+9330T>C		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+9330T>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-22+8649T>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37131 AN: 151860 Hom.: 5127 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37168 AN: 151978 Hom.: 5133 Cov.: 31 AF XY: 0.245 AC XY: 18183 AN XY: 74270

African (AFR) AF: 0.144 AC: 5954 AN: 41486

American (AMR) AF: 0.231 AC: 3533 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3468

East Asian (EAS) AF: 0.0530 AC: 275 AN: 5186

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4812

European-Finnish (FIN) AF: 0.348 AC: 3659 AN: 10528

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20660 AN: 67914

Other (OTH) AF: 0.245 AC: 518 AN: 2112

Alfa AF: 0.272 Hom.: 1421

Bravo AF: 0.230

Asia WGS AF: 0.255 AC: 880 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		1.1
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: rs1013402; hg19: chr11-27712381;