11-27699390-C-G

Position:

• chr11-27699390-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000395986.6(BDNF):​c.16G>C​(p.Glu6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E6K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BDNF ENST00000395986.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11542067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+774G>C		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+774G>C		intron_variant		1	NM_001709.5	ENSP00000349084	P4
	ENST00000530663.1	n.148-2868G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.4
DANN	Benign	0.75
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN	Benign	0.10	N
REVEL	Benign	0.053
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.76	T
Polyphen		0.94	P
Vest4		0.094
MutPred		0.16		Gain of MoRF binding (P = 0.0189);
MVP		0.48
ClinPred		0.94	D
GERP RS		0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs66866077; hg19: chr11-27720937;