rs2049046

Positions:

• chr11-27702228-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000530663.1(ENSG00000255496):​n.148-5706A>T variant causes a intron, non coding transcript 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: ENST00000530663.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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 -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/exons	MANE	Protein	UniProt
BDNF	NM_001143805.1	c.-22+18416A>T		intron_variant			NP_001137277.1
BDNF	NM_001143806.1	c.-22+18201A>T		intron_variant			NP_001137278.1
BDNF	NM_001143807.2	c.-22+17283A>T		intron_variant			NP_001137279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000530663.1	n.148-5706A>T		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.481

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2049046; hg19: chr11-27723775;