11-27657844-A-C

Variant names:

• chr11-27657844-A-C
• rs1852776284
• NM_001709.5:c.721T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001709.5(BDNF):​c.721T>G​(p.Leu241Val) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BDNF NM_001709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.721T>G	p.Leu241Val	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.721T>G	p.Leu241Val	missense_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.721T>G	p.Leu241Val	missense_variant	Exon 2 of 2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Uncertain	0.49	T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen	Benign	0.080
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.99	.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	2.0	M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Vest4		0.69
MutPred		0.78		Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);.;Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);.;Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);Gain of methylation at K244 (P = 0.0526);.;
MVP		0.82
MPC		1.1
ClinPred		0.92	D
GERP RS		-5.1
Varity_R		0.86
gMVP		0.77

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

LitVar

Other links and lift over

dbSNP: rs1852776284; hg19: chr11-27679391;