11-27655494-C-T

Position:

• chr11-27655494-C-T

Variant summary

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

The NM_001709.5(BDNF):​c.*2327G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,022 control chromosomes in the GnomAD database, including 33,832 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 0.66 (33831 hom., cov: 32)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.*2327G>A		3_prime_UTR_variant	2/2	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.*2327G>A		3_prime_UTR_variant	2/2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.*2327G>A		3_prime_UTR_variant	2/2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100442 AN: 151896 Hom.: 33824 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.661 AC: 100467 AN: 152014 Hom.: 33831 Cov.: 32 AF XY: 0.664 AC XY: 49304 AN XY: 74302

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.682

Alfa AF: 0.700 Hom.: 35391

Bravo AF: 0.663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.4
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7124442; hg19: chr11-27677041;