rs28383487

Positions:

• chr11-27722009-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_170731.5(BDNF):​c.-595C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,640 control chromosomes in the GnomAD database, including 45 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 0.015 (45 hom., cov: 31)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: BDNF NM_170731.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661

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]

ENSG00000255496 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BS2: High AC in GnomAd4 at 2273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_170731.5	c.-595C>A		5_prime_UTR_variant	1/2		NP_733927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000314915.6	c.-595C>A		5_prime_UTR_variant	1/2	1		ENSP00000320002.6
ENSG00000255496	ENST00000530663.1	n.148-25487C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2274 AN: 151910 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0114 AC: 7 AN: 616 Hom.: 0 Cov.: 0 AF XY: 0.0155 AC XY: 5 AN XY: 322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0150 AC: 2273 AN: 152024 Hom.: 45 Cov.: 31 AF XY: 0.0163 AC XY: 1209 AN XY: 74270

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.00851

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0166 Hom.: 9

Bravo AF: 0.0107

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28383487; hg19: chr11-27743556;