rs11030099

Positions:

• chr11-27656036-C-A

Variant summary

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

The NM_001709.5(BDNF):​c.*1785G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,984 control chromosomes in the GnomAD database, including 2,880 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 0.17 (2880 hom., cov: 31)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.*1785G>T		3_prime_UTR_variant	2/2	ENST00000356660.9	NP_001700.2
BDNF-AS	NR_033312.1	n.306-2205C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.*1785G>T		3_prime_UTR_variant	2/2	1	NM_001709.5	ENSP00000349084	P4
BDNF-AS	ENST00000651238.1	n.380-2205C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26115 AN: 151824 Hom.: 2882 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.100 AC: 4 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0769 AC XY: 2 AN XY: 26

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.172 AC: 26109 AN: 151944 Hom.: 2880 Cov.: 31 AF XY: 0.173 AC XY: 12874 AN XY: 74260

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.188

Alfa AF: 0.144 Hom.: 443

Bravo AF: 0.171

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.4
DANN	Benign	0.74

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: rs11030099; hg19: chr11-27677583;