rs11030107

Variant names:

• chr11-27673288-A-G
• rs11030107
• NM_001709.5:c.-21-14703T>C

Variant summary

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

The NM_001709.5(BDNF):​c.-21-14703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,440 control chromosomes in the GnomAD database, including 3,061 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 0.19 (3061 hom., cov: 31)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 28 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-14703T>C		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.-21-14703T>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-14703T>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28143 AN: 151356 Hom.: 3060 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.186 AC: 28151 AN: 151440 Hom.: 3061 Cov.: 31 AF XY: 0.180 AC XY: 13348 AN XY: 73954

African (AFR) AF: 0.103 AC: 4265 AN: 41254

American (AMR) AF: 0.188 AC: 2858 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3470

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5164

South Asian (SAS) AF: 0.108 AC: 519 AN: 4788

European-Finnish (FIN) AF: 0.248 AC: 2571 AN: 10352

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.248 AC: 16836 AN: 67886

Other (OTH) AF: 0.194 AC: 409 AN: 2106

Alfa AF: 0.202 Hom.: 447

Bravo AF: 0.182

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		-0.29
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: rs11030107; hg19: chr11-27694835;