rs10835211

Positions:

• chr11-27679818-G-A

Variant summary

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

The NM_001709.5(BDNF):​c.-22+20346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,242 control chromosomes in the GnomAD database, including 3,011 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 0.18 (3011 hom., cov: 33)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+20346C>T		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+20346C>T		intron_variant		1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-22+19665C>T		intron_variant		1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27792 AN: 152124 Hom.: 3011 Cov.: 33

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.183 AC: 27797 AN: 152242 Hom.: 3011 Cov.: 33 AF XY: 0.177 AC XY: 13165 AN XY: 74450

Gnomad4 AFR AF: 0.0973

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.194

Alfa AF: 0.224 Hom.: 7921

Bravo AF: 0.179

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10835211; hg19: chr11-27701365;