rs3750934

Variant names:

• chr11-27658648-A-G
• rs3750934
• NM_001709.5:c.-21-63T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_170735.6(BDNF):​c.-84T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,613,506 control chromosomes in the GnomAD database, including 56 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 0.0039 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (44 hom.)
• Consequence: BDNF NM_170735.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.91).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00394 (601/152350) while in subpopulation EAS AF= 0.0245 (127/5184). AF 95% confidence interval is 0.021. There are 12 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 601 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-63T>C		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.-21-63T>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-63T>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 600 AN: 152232 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00218 AC: 3182 AN: 1461156 Hom.: 44 Cov.: 33 AF XY: 0.00208 AC XY: 1514 AN XY: 726844

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0193

Gnomad4 SAS exome AF: 0.000570

Gnomad4 FIN exome AF: 0.0355

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00394 AC: 601 AN: 152350 Hom.: 12 Cov.: 32 AF XY: 0.00540 AC XY: 402 AN XY: 74492

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00117

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.42

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: rs3750934; hg19: chr11-27680195;