rs2030324

Positions:

• chr11-27705368-A-G

Variant summary

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

The ENST00000314915.6(BDNF):​c.3+16044T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,994 control chromosomes in the GnomAD database, including 18,126 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 0.49 (18126 hom., cov: 32)
• Consequence: BDNF ENST00000314915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001143805.1	c.-22+15276T>C		intron_variant			NP_001137277.1
BDNF	NM_001143806.1	c.-22+15061T>C		intron_variant			NP_001137278.1
BDNF	NM_001143807.2	c.-22+14143T>C		intron_variant			NP_001137279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000530663.1	n.148-8846T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73747 AN: 151876 Hom.: 18123 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.485 AC: 73775 AN: 151994 Hom.: 18126 Cov.: 32 AF XY: 0.487 AC XY: 36142 AN XY: 74276

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.485

Alfa AF: 0.497 Hom.: 2435

Bravo AF: 0.489

Asia WGS AF: 0.378 AC: 1313 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2030324; hg19: chr11-27726915;