rs13306221

Positions:

• chr11-27701142-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000530663.1(ENSG00000255496):​n.148-4620G>A 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 0.0698 in 1,246,492 control chromosomes in the GnomAD database, including 4,614 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 0.061 (404 hom., cov: 32)
  • Exomes 𝑓: 0.071 (4210 hom.)
• Consequence: ENST00000530663.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001143805.1	c.-22+19502G>A		intron_variant			NP_001137277.1
BDNF	NM_001143806.1	c.-22+19287G>A		intron_variant			NP_001137278.1
BDNF	NM_001143807.2	c.-22+18369G>A		intron_variant			NP_001137279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000530663.1	n.148-4620G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9284 AN: 152114 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0531

GnomAD4 exome AF: 0.0710 AC: 77729 AN: 1094260 Hom.: 4210 Cov.: 18 AF XY: 0.0779 AC XY: 41724 AN XY: 535882

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.0373

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.0923

Gnomad4 NFE exome AF: 0.0583

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0612 AC: 9314 AN: 152232 Hom.: 404 Cov.: 32 AF XY: 0.0666 AC XY: 4961 AN XY: 74454

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.0979

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0607 Hom.: 66

Bravo AF: 0.0512

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
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: rs13306221; hg19: chr11-27722689;