rs28722151

Variant names:

• chr11-27659629-C-A
• rs28722151
• ENST00000439476.6:c.-831G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-27659629-C-A
• chr11-27659629-C-G
• chr11-27659629-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000439476.6(BDNF):​c.-831G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 831,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: BDNF ENST00000439476.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-1044G>T		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.-21-1044G>T		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-1044G>T		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000241 AC: 2 AN: 831288 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 384376

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15034

American (AMR) AF: 0.00 AC: 0 AN: 960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5084

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 16198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1588

European-Non Finnish (NFE) AF: 0.00000268 AC: 2 AN: 747318

Other (OTH) AF: 0.00 AC: 0 AN: 26870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.64
PhyloP100		-0.34
PromoterAI		-0.027	Neutral

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: rs28722151; hg19: chr11-27681176;