rs199638553

Variant names:

• chr11-27658332-C-A
• NM_001709.5:c.233G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-27658332-C-A
• chr11-27658332-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001709.5(BDNF):​c.233G>T​(p.Arg78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: BDNF NM_001709.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18308547).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.233G>T	p.Arg78Leu	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.233G>T	p.Arg78Leu	missense_variant	Exon 2 of 2	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.233G>T	p.Arg78Leu	missense_variant	Exon 2 of 2	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.40	T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	.;.;D;.;.;.;.;.;.;D;D;.;.;.;.;.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;L;.;L;L;L;L;L;L;.;L;L;L;L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.90	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0020	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.37	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.65	P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
Vest4		0.14
MutPred		0.33		Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);.;Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);.;Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);Loss of ubiquitination at K76 (P = 0.0454);.;
MVP		0.46
MPC		0.96
ClinPred		0.59	D
GERP RS		4.1
Varity_R		0.12
gMVP		0.38

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: chr11-27679879;