chr11-27672694-G-C

Variant names:

• chr11-27672694-G-C
• rs2049045
• NM_001709.5:c.-21-14109C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.-21-14109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,150 control chromosomes in the GnomAD database, including 1,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.13 (1726 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 44 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]

BDNF-AS (HGNC:20608): (BDNF antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-14109C>G		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-14109C>G		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-14109C>G		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19065 AN: 152032 Hom.: 1726 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.125 AC: 19058 AN: 152150 Hom.: 1726 Cov.: 32 AF XY: 0.122 AC XY: 9048 AN XY: 74380

African (AFR) AF: 0.0334 AC: 1388 AN: 41522

American (AMR) AF: 0.128 AC: 1956 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0482 AC: 232 AN: 4812

European-Finnish (FIN) AF: 0.148 AC: 1568 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12537 AN: 67982

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.0832 Hom.: 125

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		0.71
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: rs2049045; hg19: chr11-27694241;