11-27673917-A-G

Position:

• chr11-27673917-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001709.5(BDNF):​c.-21-15332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 976,550 control chromosomes in the GnomAD database, including 246,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40334 hom., cov: 31)
  • Exomes 𝑓: 0.70 (206569 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.517

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-27673917-A-G is Benign according to our data. Variant chr11-27673917-A-G is described in ClinVar as [Benign]. Clinvar id is 1238836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-15332T>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.-21-15332T>C		intron_variant		1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-15332T>C		intron_variant		1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110257 AN: 151846 Hom.: 40313 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.703 AC: 580001 AN: 824586 Hom.: 206569 AF XY: 0.703 AC XY: 289105 AN XY: 411006

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.966

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.688

Gnomad4 OTH exome AF: 0.722

GnomAD4 genome AF: 0.726 AC: 110326 AN: 151964 Hom.: 40334 Cov.: 31 AF XY: 0.728 AC XY: 54052 AN XY: 74274

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.733

Alfa AF: 0.714 Hom.: 52804

Bravo AF: 0.736

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11030108; hg19: chr11-27695464;