rs2883187

chr11-27719545-G-Achr11-27719545-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000532997.5(BDNF):c.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 984,812 control chromosomes in the GnomAD database, including 104,789 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 0.41 (13988 hom., cov: 29)
  • Exomes 𝑓: 0.46 (90801 hom.)
• Consequence: BDNF ENST00000532997.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001143807.2	c.-56C>T		5_prime_UTR_variant	1/2
BDNF	NM_001143805.1	c.-22+1099C>T		intron_variant
BDNF	NM_001143806.1	c.-22+884C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000530663.1	n.148-23023C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61801 AN: 151492 Hom.: 13987 Cov.: 29

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.464 AC: 386611 AN: 833200 Hom.: 90801 Cov.: 31 AF XY: 0.464 AC XY: 178628 AN XY: 384802

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.408 AC: 61811 AN: 151612 Hom.: 13988 Cov.: 29 AF XY: 0.411 AC XY: 30441 AN XY: 74060

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.430

Alfa AF: 0.335 Hom.: 1015

Bravo AF: 0.403

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	16
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2883187; hg19: chr11-27741092;