11-27659197-A-T

Variant names:

• chr11-27659197-A-T
• rs11030101
• ENST00000439476.6:c.-399T>A

Variant summary

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

The NM_170735.6(BDNF):​c.-633T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 996,850 control chromosomes in the GnomAD database, including 98,075 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 0.36 (11403 hom., cov: 31)
  • Exomes 𝑓: 0.45 (86672 hom.)
• Consequence: BDNF NM_170735.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 74 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 (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170735.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-21-612T>A		intron	N/A	NP_001700.2
	BDNF	NM_001143816.2		c.-399T>A		5_prime_UTR	Exon 1 of 2	NP_001137288.1	P23560-1
	BDNF	NM_170735.6		c.-633T>A		5_prime_UTR	Exon 1 of 1	NP_733931.1	A0A0E3SU01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000439476.6	TSL:1	c.-399T>A		5_prime_UTR	Exon 1 of 2	ENSP00000389345.2	P23560-1
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-612T>A		intron	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.226-612T>A		intron	N/A	ENSP00000414303.1	P23560-4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54900 AN: 151888 Hom.: 11404 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.449 AC: 379482 AN: 844846 Hom.: 86672 Cov.: 29 AF XY: 0.450 AC XY: 175698 AN XY: 390442

African (AFR) AF: 0.147 AC: 2314 AN: 15736

American (AMR) AF: 0.312 AC: 328 AN: 1052

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 2596 AN: 5128

East Asian (EAS) AF: 0.266 AC: 965 AN: 3628

South Asian (SAS) AF: 0.312 AC: 5122 AN: 16412

European-Finnish (FIN) AF: 0.482 AC: 7223 AN: 14976

Middle Eastern (MID) AF: 0.481 AC: 777 AN: 1616

European-Non Finnish (NFE) AF: 0.459 AC: 348253 AN: 758982

Other (OTH) AF: 0.436 AC: 11904 AN: 27316

GnomAD4 genome AF: 0.361 AC: 54898 AN: 152004 Hom.: 11403 Cov.: 31 AF XY: 0.360 AC XY: 26782 AN XY: 74292

African (AFR) AF: 0.169 AC: 7011 AN: 41496

American (AMR) AF: 0.318 AC: 4866 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1412 AN: 5146

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4814

European-Finnish (FIN) AF: 0.482 AC: 5085 AN: 10554

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31921 AN: 67930

Other (OTH) AF: 0.386 AC: 817 AN: 2114

Alfa AF: 0.420 Hom.: 1824

Bravo AF: 0.339

Asia WGS AF: 0.292 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.7
DANN	Benign	0.87
PhyloP100		-0.19
PromoterAI		0.0056	Neutral
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: rs11030101; hg19: chr11-27680744;