rs6484320

chr11-27681641-T-Achr11-27681641-T-Cchr11-27681641-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BDNF	NM_001709.5	c.-22+18523A>T		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.1307+4502T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+18523A>T		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.817+4502T>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.800

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6484320; hg19: chr11-27703188;