NM_001709.5:c.164G>T

Variant names:

• chr11-27658401-C-A
• NM_001709.5:c.164G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001709.5(BDNF):​c.164G>T​(p.Gly55Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BDNF NM_001709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26983887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.164G>T	p.Gly55Val	missense_variant	Exon 2 of 2	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.164G>T	p.Gly55Val	missense_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.164G>T	p.Gly55Val	missense_variant	Exon 2 of 2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164G>T (p.G55V) alteration is located in exon 1 (coding exon 1) of the BDNF gene. This alteration results from a G to T substitution at nucleotide position 164, causing the glycine (G) at amino acid position 55 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.98	.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.5	M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.59	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.98	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Vest4		0.22
MutPred		0.40		Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);.;Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);.;Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);Loss of disorder (P = 0.0373);.;
MVP		0.67
MPC		1.8
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27679948;