11-27705368-A-G

Variant names:

• chr11-27705368-A-G
• rs2030324
• ENST00000314915.6:c.3+16044T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 169 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=-0.88).
• 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 rank	MANE	Protein	UniProt
BDNF	NM_170731.5	c.3+16044T>C		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+15276T>C		intron_variant	Intron 1 of 1		NP_001137277.1
BDNF	NM_001143806.1	c.-22+15061T>C		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+16044T>C		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+15061T>C		intron_variant	Intron 1 of 1	1		ENSP00000379302.3
BDNF	ENST00000395981.7	c.-22+14978T>C		intron_variant	Intron 1 of 1	1		ENSP00000379305.3

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

African (AFR) AF: 0.476 AC: 19743 AN: 41458

American (AMR) AF: 0.550 AC: 8411 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2292 AN: 5158

South Asian (SAS) AF: 0.333 AC: 1606 AN: 4826

European-Finnish (FIN) AF: 0.506 AC: 5350 AN: 10564

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33008 AN: 67928

Other (OTH) AF: 0.485 AC: 1022 AN: 2108

Alfa AF: 0.484 Hom.: 26141

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
PhyloP100		0.63
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: rs2030324; hg19: chr11-27726915;