11-27660309-C-T

Variant names:

• chr11-27660309-C-T
• rs57083135
• NM_001709.5:c.-21-1724G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.-21-1724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 983,374 control chromosomes in the GnomAD database, including 293 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 0.030 (162 hom., cov: 32)
  • Exomes 𝑓: 0.011 (131 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-1724G>A		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.-21-1724G>A		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-1724G>A		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4550 AN: 152198 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0154 AC: 1687 AN: 109512 Hom.: 30 AF XY: 0.0147 AC XY: 885 AN XY: 60026

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00865

Gnomad EAS exome AF: 0.0331

Gnomad SAS exome AF: 0.0140

Gnomad FIN exome AF: 0.00596

Gnomad NFE exome AF: 0.00863

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.0109 AC: 9036 AN: 831058 Hom.: 131 Cov.: 11 AF XY: 0.0110 AC XY: 4585 AN XY: 418532

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.00924

Gnomad4 EAS exome AF: 0.0315

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.00563

Gnomad4 NFE exome AF: 0.00763

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0300 AC: 4574 AN: 152316 Hom.: 162 Cov.: 32 AF XY: 0.0293 AC XY: 2184 AN XY: 74498

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.0314

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00850

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0154 Hom.: 12

Bravo AF: 0.0334

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57083135; hg19: chr11-27681856;