11-27676827-T-C

Variant names:

• chr11-27676827-T-C
• rs16917234
• NM_001709.5:c.-21-18242A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.-21-18242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,198 control chromosomes in the GnomAD database, including 2,506 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 0.11 (2506 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-21-18242A>G		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-2485A>G		intron	N/A	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.67-18242A>G		intron	N/A	NP_001137281.1	P23560-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-18242A>G		intron	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.-58-2485A>G		intron	N/A	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.25-18242A>G		intron	N/A	ENSP00000379309.2	P23560-3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17411 AN: 152080 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00253

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.115 AC: 17441 AN: 152198 Hom.: 2506 Cov.: 32 AF XY: 0.116 AC XY: 8637 AN XY: 74432

African (AFR) AF: 0.306 AC: 12716 AN: 41492

American (AMR) AF: 0.224 AC: 3421 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.164 AC: 851 AN: 5182

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00253 AC: 172 AN: 68030

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.142 Hom.: 1330

Bravo AF: 0.142

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.62
PhyloP100		-0.46
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: rs16917234; hg19: chr11-27698374;