rs11030102

Positions:

• chr11-27660049-C-G

Variant summary

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

The NM_001709.5(BDNF):​c.-21-1464G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 387,484 control chromosomes in the GnomAD database, including 9,716 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 0.19 (3090 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6626 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-1464G>C		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-1464G>C		intron_variant		1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-1464G>C		intron_variant		1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28281 AN: 152004 Hom.: 3089 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.229 AC: 53864 AN: 235362 Hom.: 6626 AF XY: 0.221 AC XY: 26562 AN XY: 120420

Gnomad4 AFR exome AF: 0.0985

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.00321

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.186 AC: 28287 AN: 152122 Hom.: 3090 Cov.: 32 AF XY: 0.181 AC XY: 13446 AN XY: 74372

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.194

Alfa AF: 0.207 Hom.: 442

Bravo AF: 0.182

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11030102; hg19: chr11-27681596;