chr11-27712873-T-C

Variant names:

• chr11-27712873-T-C
• rs962369
• ENST00000314915.6:c.3+8539A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-0.91).
• 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 rank	MANE	Protein	UniProt
BDNF	NM_170731.5	c.3+8539A>G		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+7771A>G		intron_variant	Intron 1 of 1		NP_001137277.1
BDNF	NM_001143806.1	c.-22+7556A>G		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+8539A>G		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+7556A>G		intron_variant	Intron 1 of 1	1		ENSP00000379302.3
BDNF	ENST00000395981.7	c.-22+7473A>G		intron_variant	Intron 1 of 1	1		ENSP00000379305.3

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

African (AFR) AF: 0.157 AC: 6448 AN: 40980

American (AMR) AF: 0.224 AC: 3390 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3464

East Asian (EAS) AF: 0.0517 AC: 265 AN: 5124

South Asian (SAS) AF: 0.348 AC: 1663 AN: 4772

European-Finnish (FIN) AF: 0.330 AC: 3315 AN: 10038

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19750 AN: 67798

Other (OTH) AF: 0.244 AC: 507 AN: 2082

Alfa AF: 0.262 Hom.: 15463

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
PhyloP100		0.50
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: rs962369; hg19: chr11-27734420;