rs56164415

Positions:

• chr11-27700188-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-46C>T		5_prime_UTR_variant	1/2	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-46C>T		5_prime_UTR_variant	1/2	1	NM_001709.5	ENSP00000349084	P4
	ENST00000530663.1	n.148-3666C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0526

Gnomad4 EAS exome AF: 0.0344

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.0587

Gnomad4 OTH exome AF: 0.0748

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

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0428

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0598 Hom.: 68

Bravo AF: 0.0511

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Variant of unknown significance Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 15, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56164415; hg19: chr11-27721735;