11-27656036-C-A

Variant names:

• chr11-27656036-C-A
• rs11030099
• ENST00000530786.5:n.*2658G>T

Variant summary

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

The NM_001709.5(BDNF):​c.*1785G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,984 control chromosomes in the GnomAD database, including 2,880 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 0.17 (2880 hom., cov: 31)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 25 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.*1785G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.*1785G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.*1785G>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26115 AN: 151824 Hom.: 2882 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.100 AC: 4 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0769 AC XY: 2 AN XY: 26

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0357 AC: 1 AN: 28

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.172 AC: 26109 AN: 151944 Hom.: 2880 Cov.: 31 AF XY: 0.173 AC XY: 12874 AN XY: 74260

African (AFR) AF: 0.0624 AC: 2589 AN: 41514

American (AMR) AF: 0.179 AC: 2728 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3462

East Asian (EAS) AF: 0.465 AC: 2368 AN: 5096

South Asian (SAS) AF: 0.263 AC: 1262 AN: 4804

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13778 AN: 67928

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.142 Hom.: 444

Bravo AF: 0.171

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.4
DANN	Benign	0.74
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11030099; hg19: chr11-27677583;