11-27678770-G-C

Position:

• chr11-27678770-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.-21-20185C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,860 control chromosomes in the GnomAD database, including 17,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17577 hom., cov: 31)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001709.5	c.-21-20185C>G		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.1307+1631G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-20185C>G		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.817+1631G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72600 AN: 151742 Hom.: 17573 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.478 AC: 72629 AN: 151860 Hom.: 17577 Cov.: 31 AF XY: 0.480 AC XY: 35630 AN XY: 74186

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.481

Alfa AF: 0.480 Hom.: 2138

Bravo AF: 0.481

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7103873; hg19: chr11-27700317;