rs7103411

Variant names:

• chr11-27678578-C-T
• rs7103411
• NM_001709.5:c.-21-19993G>A

Variant summary

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

The NM_001709.5(BDNF):​c.-21-19993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,202 control chromosomes in the GnomAD database, including 51,299 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 0.82 (51299 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 103 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 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.-21-19993G>A		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-4236G>A		intron	N/A	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.67-19993G>A		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.-21-19993G>A		intron	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.-58-4236G>A		intron	N/A	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.25-19993G>A		intron	N/A	ENSP00000379309.2	P23560-3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124060 AN: 152084 Hom.: 51240 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.816 AC: 124181 AN: 152202 Hom.: 51299 Cov.: 32 AF XY: 0.814 AC XY: 60572 AN XY: 74406

African (AFR) AF: 0.917 AC: 38116 AN: 41548

American (AMR) AF: 0.816 AC: 12479 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2459 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2716 AN: 5142

South Asian (SAS) AF: 0.695 AC: 3353 AN: 4826

European-Finnish (FIN) AF: 0.838 AC: 8883 AN: 10602

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53649 AN: 68004

Other (OTH) AF: 0.800 AC: 1693 AN: 2116

Alfa AF: 0.793 Hom.: 136003

Bravo AF: 0.818

Asia WGS AF: 0.678 AC: 2359 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		-0.028
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: rs7103411; hg19: chr11-27700125;