rs962369

chr11-27712873-T-Cchr11-27712873-T-G

Variant summary

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

The ENST00000314915.6(BDNF):c.3+8539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 150,562 control chromosomes in the GnomAD database, including 4,807 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 0.24 (4807 hom., cov: 29)
• Consequence: BDNF ENST00000314915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001143805.1	c.-22+7771A>G		intron_variant
BDNF	NM_001143806.1	c.-22+7556A>G		intron_variant
BDNF	NM_001143807.2	c.-22+6638A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000530663.1	n.148-16351A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36171 AN: 150460 Hom.: 4802 Cov.: 29

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.240 AC: 36202 AN: 150562 Hom.: 4807 Cov.: 29 AF XY: 0.240 AC XY: 17625 AN XY: 73370

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.244

Alfa AF: 0.264 Hom.: 5460

Bravo AF: 0.228

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.8
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: rs962369; hg19: chr11-27734420;