rs56820186

Variant names:

• chr11-27657465-T-G
• rs56820186
• NM_001709.5:c.*356A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.*356A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 936,852 control chromosomes in the GnomAD database, including 274 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 0.13 (169 hom., cov: 0)
  • Exomes 𝑓: 0.010 (105 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 3 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]

BDNF-AS (HGNC:20608): (BDNF antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 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.*356A>C		3_prime_UTR	Exon 2 of 2	NP_001700.2
	BDNF	NM_001143810.2		c.*356A>C		3_prime_UTR	Exon 3 of 3	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.*356A>C		3_prime_UTR	Exon 2 of 2	NP_001137281.1	P23560-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.*356A>C		3_prime_UTR	Exon 2 of 2	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.*356A>C		3_prime_UTR	Exon 3 of 3	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.*356A>C		3_prime_UTR	Exon 2 of 2	ENSP00000379309.2	P23560-3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 4625 AN: 34456 Hom.: 161 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.0102 AC: 9214 AN: 902298 Hom.: 105 Cov.: 32 AF XY: 0.0102 AC XY: 4310 AN XY: 421456

African (AFR) AF: 0.0906 AC: 1559 AN: 17214

American (AMR) AF: 0.0116 AC: 56 AN: 4848

Ashkenazi Jewish (ASJ) AF: 0.00945 AC: 65 AN: 6880

East Asian (EAS) AF: 0.0293 AC: 216 AN: 7360

South Asian (SAS) AF: 0.0148 AC: 386 AN: 26096

European-Finnish (FIN) AF: 0.00486 AC: 17 AN: 3500

Middle Eastern (MID) AF: 0.0448 AC: 83 AN: 1852

European-Non Finnish (NFE) AF: 0.00784 AC: 6304 AN: 803728

Other (OTH) AF: 0.0171 AC: 528 AN: 30820

GnomAD4 genome AF: 0.135 AC: 4653 AN: 34554 Hom.: 169 Cov.: 0 AF XY: 0.132 AC XY: 2217 AN XY: 16810

African (AFR) AF: 0.175 AC: 3356 AN: 19190

American (AMR) AF: 0.0744 AC: 308 AN: 4138

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 46 AN: 206

East Asian (EAS) AF: 0.296 AC: 160 AN: 540

South Asian (SAS) AF: 0.0825 AC: 68 AN: 824

European-Finnish (FIN) AF: 0.0353 AC: 49 AN: 1390

Middle Eastern (MID) AF: 0.289 AC: 11 AN: 38

European-Non Finnish (NFE) AF: 0.0753 AC: 581 AN: 7718

Other (OTH) AF: 0.142 AC: 61 AN: 430

Alfa AF: 0.0184 Hom.: 99

Bravo AF: 0.0340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56820186; hg19: chr11-27679012;