11-27679818-G-A

Variant names:

• chr11-27679818-G-A
• rs10835211
• NM_001709.5:c.-22+20346C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-22+20346C>T		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-5476C>T		intron	N/A	NP_001137282.1
	BDNF	NM_001143809.2		c.66+21153C>T		intron	N/A	NP_001137281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-22+20346C>T		intron	N/A	ENSP00000349084.4
	BDNF	ENST00000438929.5	TSL:1	c.-58-5476C>T		intron	N/A	ENSP00000414303.1
	BDNF	ENST00000395986.6	TSL:1	c.24+19564C>T		intron	N/A	ENSP00000379309.2

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

African (AFR) AF: 0.0973 AC: 4040 AN: 41538

American (AMR) AF: 0.187 AC: 2857 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5186

South Asian (SAS) AF: 0.108 AC: 523 AN: 4830

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16797 AN: 68010

Other (OTH) AF: 0.194 AC: 410 AN: 2116

Alfa AF: 0.219 Hom.: 11776

Bravo AF: 0.179

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		0.57
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: rs10835211; hg19: chr11-27701365;