rs28722151

Positions:

• chr11-27659629-C-G
• chr11-27659629-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170735.6(BDNF):​c.-1065G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,392 control chromosomes in the GnomAD database, including 10,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10474 hom., cov: 29)
  • Exomes 𝑓: 0.43 (77140 hom.)
  • Failed GnomAD Quality Control
• Consequence: BDNF NM_170735.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-27659629-C-G is Benign according to our data. Variant chr11-27659629-C-G is described in ClinVar as [Benign]. Clinvar id is 1258199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-1044G>C		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-1044G>C		intron_variant		1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-1044G>C		intron_variant		1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52509 AN: 151276 Hom.: 10476 Cov.: 29

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.362

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.432 AC: 359240 AN: 831212 Hom.: 77140 Cov.: 36 AF XY: 0.432 AC XY: 166012 AN XY: 384334

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.347 AC: 52508 AN: 151392 Hom.: 10474 Cov.: 29 AF XY: 0.347 AC XY: 25675 AN XY: 73962

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.363

Alfa AF: 0.318 Hom.: 674

Bravo AF: 0.325

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.52

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: rs28722151; hg19: chr11-27681176;