11-27659197-A-G

Variant names:

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

Variant summary

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

The NM_170735.6(BDNF):​c.-633T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 845,534 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: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: BDNF NM_170735.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 71 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=-0.66).

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>C		intron	N/A	NP_001700.2
	BDNF	NM_001143816.2		c.-399T>C		5_prime_UTR	Exon 1 of 2	NP_001137288.1	P23560-1
	BDNF	NM_170735.6		c.-633T>C		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>C		5_prime_UTR	Exon 1 of 2	ENSP00000389345.2	P23560-1
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-612T>C		intron	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.226-612T>C		intron	N/A	ENSP00000414303.1	P23560-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 845534 Hom.: 0 Cov.: 29 AF XY: 0.00000256 AC XY: 1 AN XY: 390744

African (AFR) AF: 0.00 AC: 0 AN: 15746

American (AMR) AF: 0.00 AC: 0 AN: 1052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5134

East Asian (EAS) AF: 0.00 AC: 0 AN: 3634

South Asian (SAS) AF: 0.00 AC: 0 AN: 16422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1618

European-Non Finnish (NFE) AF: 0.00000132 AC: 1 AN: 759624

Other (OTH) AF: 0.00 AC: 0 AN: 27328

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		-0.19
PromoterAI		0.0080	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: rs11030101; hg19: chr11-27680744;