rs7127507

chr11-27693337-T-C

Variant summary

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

The NM_001709.5(BDNF):c.-22+6827A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,050 control chromosomes in the GnomAD database, including 9,339 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 0.34 (9339 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDNF	NM_001709.5	c.-22+6827A>G		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.1342+2197T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+6827A>G		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.818-4141T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51533 AN: 151930 Hom.: 9299 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.340 AC: 51626 AN: 152050 Hom.: 9339 Cov.: 32 AF XY: 0.337 AC XY: 25021 AN XY: 74334

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.319

Alfa AF: 0.318 Hom.: 2233

Bravo AF: 0.338

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.0
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7127507; hg19: chr11-27714884;