rs2049046

Variant names:

• chr11-27702228-T-A
• rs2049046
• ENST00000314915.6:c.3+19184A>T

Variant summary

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

The ENST00000314915.6(BDNF):​c.3+19184A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,024 control chromosomes in the GnomAD database, including 17,422 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 0.48 (17422 hom., cov: 32)
• Consequence: BDNF ENST00000314915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 71 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_170731.5	c.3+19184A>T		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+18416A>T		intron_variant	Intron 1 of 1		NP_001137277.1
BDNF	NM_001143806.1	c.-22+18201A>T		intron_variant	Intron 1 of 1		NP_001137278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000314915.6	c.3+19184A>T		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+18201A>T		intron_variant	Intron 1 of 1	1		ENSP00000379302.3
BDNF	ENST00000395981.7	c.-22+18118A>T		intron_variant	Intron 1 of 1	1		ENSP00000379305.3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72318 AN: 151906 Hom.: 17418 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.476 AC: 72346 AN: 152024 Hom.: 17422 Cov.: 32 AF XY: 0.477 AC XY: 35432 AN XY: 74290

African (AFR) AF: 0.474 AC: 19659 AN: 41440

American (AMR) AF: 0.542 AC: 8287 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2294 AN: 5162

South Asian (SAS) AF: 0.327 AC: 1575 AN: 4818

European-Finnish (FIN) AF: 0.483 AC: 5097 AN: 10556

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32111 AN: 67986

Other (OTH) AF: 0.481 AC: 1015 AN: 2110

Alfa AF: 0.486 Hom.: 2243

Bravo AF: 0.480

Asia WGS AF: 0.376 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.8
DANN	Benign	0.71
PhyloP100		0.36
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: rs2049046; hg19: chr11-27723775;