rs56164415

Variant names:

• chr11-27700188-G-A
• rs56164415
• NM_001709.5:c.-46C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001709.5(BDNF):​c.-46C>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 0.0625 in 985,630 control chromosomes in the GnomAD database, including 2,438 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.061 (400 hom., cov: 32)
  • Exomes 𝑓: 0.063 (2038 hom.)
• Consequence: BDNF NM_001709.5 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.49
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 2	NP_001700.2
	BDNF	NM_001143813.2		c.-28C>T		5_prime_UTR	Exon 1 of 2	NP_001137285.1	P23560-1
	BDNF	NM_001143814.2		c.-153C>T		5_prime_UTR	Exon 1 of 3	NP_001137286.1	P23560-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-46C>T		5_prime_UTR	Exon 1 of 2	ENSP00000349084.4	P23560-1
	BDNF	ENST00000418212.5	TSL:1	c.-153C>T		5_prime_UTR	Exon 1 of 3	ENSP00000400502.1	P23560-1
	BDNF	ENST00000533246.5	TSL:1	c.-28C>T		5_prime_UTR	Exon 1 of 2	ENSP00000432376.1	P23560-1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9264 AN: 152076 Hom.: 396 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0628 AC: 52326 AN: 833438 Hom.: 2038 Cov.: 28 AF XY: 0.0637 AC XY: 24503 AN XY: 384956

African (AFR) AF: 0.0507 AC: 800 AN: 15792

American (AMR) AF: 0.0345 AC: 34 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.0526 AC: 271 AN: 5154

East Asian (EAS) AF: 0.0344 AC: 125 AN: 3638

South Asian (SAS) AF: 0.255 AC: 4200 AN: 16472

European-Finnish (FIN) AF: 0.0857 AC: 24 AN: 280

Middle Eastern (MID) AF: 0.0782 AC: 127 AN: 1624

European-Non Finnish (NFE) AF: 0.0587 AC: 44702 AN: 762178

Other (OTH) AF: 0.0748 AC: 2043 AN: 27314

GnomAD4 genome AF: 0.0611 AC: 9294 AN: 152192 Hom.: 400 Cov.: 32 AF XY: 0.0664 AC XY: 4943 AN XY: 74406

African (AFR) AF: 0.0472 AC: 1960 AN: 41542

American (AMR) AF: 0.0423 AC: 648 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3472

East Asian (EAS) AF: 0.0428 AC: 220 AN: 5142

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4822

European-Finnish (FIN) AF: 0.0976 AC: 1035 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0574 AC: 3900 AN: 67988

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0593 Hom.: 68

Bravo AF: 0.0511

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Variant of unknown significance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		2.5
PromoterAI		0.070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs56164415; hg19: chr11-27721735;