11-27678770-G-C

Variant names:

• chr11-27678770-G-C
• rs7103873
• NM_001709.5:c.-21-20185C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-21-20185C>G		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-4428C>G		intron	N/A	NP_001137282.1
	BDNF	NM_001143809.2		c.67-20185C>G		intron	N/A	NP_001137281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-20185C>G		intron	N/A	ENSP00000349084.4
	BDNF	ENST00000438929.5	TSL:1	c.-58-4428C>G		intron	N/A	ENSP00000414303.1
	BDNF	ENST00000395986.6	TSL:1	c.25-20185C>G		intron	N/A	ENSP00000379309.2

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

African (AFR) AF: 0.475 AC: 19699 AN: 41432

American (AMR) AF: 0.543 AC: 8283 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1779 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2255 AN: 5124

South Asian (SAS) AF: 0.329 AC: 1576 AN: 4794

European-Finnish (FIN) AF: 0.507 AC: 5347 AN: 10540

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32112 AN: 67924

Other (OTH) AF: 0.481 AC: 1015 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7103873; hg19: chr11-27700317;