rs1013402

chr11-27690834-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
BDNF	NM_001709.5	c.-22+9330T>C		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.1308-272A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+9330T>C		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.818-6644A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.245

Alfa AF: 0.275 Hom.: 1415

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1013402; hg19: chr11-27712381;