11-27658244-GAG-CAA

Variant names:

• chr11-27658244-GAG-CAA
• NM_001709.5:c.319_321delCTCinsTTG
• BDNF p.108

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001709.5(BDNF):​c.319_321delCTCinsTTG​(p.108) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L107L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BDNF NM_001709.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. 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.319_321delCTCinsTTG	p.108	synonymous	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.565_567delCTCinsTTG	p.190	synonymous	N/A	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.406_408delCTCinsTTG	p.137	synonymous	N/A	NP_001137281.1	P23560-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.319_321delCTCinsTTG	p.108	synonymous	N/A	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.565_567delCTCinsTTG	p.190	synonymous	N/A	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.364_366delCTCinsTTG	p.123	synonymous	N/A	ENSP00000379309.2	P23560-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-27679791;