rs6484320

Variant names:

• chr11-27681641-T-A
• rs6484320
• NM_001709.5:c.-22+18523A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-27681641-T-A
• chr11-27681641-T-C
• chr11-27681641-T-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.-22+18523A>T 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 152,098 control chromosomes in the GnomAD database, including 51,301 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 (51301 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 21 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+18523A>T		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+18523A>T		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-22+17842A>T		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124016 AN: 151980 Hom.: 51242 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.527

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: 124137 AN: 152098 Hom.: 51301 Cov.: 32 AF XY: 0.814 AC XY: 60546 AN XY: 74362

African (AFR) AF: 0.918 AC: 38103 AN: 41528

American (AMR) AF: 0.818 AC: 12484 AN: 15254

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

East Asian (EAS) AF: 0.527 AC: 2721 AN: 5164

South Asian (SAS) AF: 0.695 AC: 3339 AN: 4806

European-Finnish (FIN) AF: 0.838 AC: 8863 AN: 10578

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

European-Non Finnish (NFE) AF: 0.789 AC: 53643 AN: 67978

Other (OTH) AF: 0.800 AC: 1690 AN: 2112

Alfa AF: 0.765 Hom.: 2352

Bravo AF: 0.818

Asia WGS AF: 0.677 AC: 2355 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		2.7
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: rs6484320; hg19: chr11-27703188;