rs10835210

chr11-27674363-C-Achr11-27674363-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001709.5(BDNF):c.-21-15778G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,518,238 control chromosomes in the GnomAD database, including 129,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9923 hom., cov: 32)
  • Exomes 𝑓: 0.41 (119966 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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=-0.39).
• BP6: Variant 11-27674363-C-A is Benign according to our data. Variant chr11-27674363-C-A is described in ClinVar as [Benign]. Clinvar id is 1276343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) 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.-21-15778G>T		intron_variant		ENST00000356660.9
BDNF-AS	NR_033312.1	n.586-1214C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-15778G>T		intron_variant		1	NM_001709.5	P4
BDNF-AS	ENST00000651238.1	n.660-2619C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50162 AN: 151908 Hom.: 9924 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.412 AC: 563187 AN: 1366212 Hom.: 119966 Cov.: 33 AF XY: 0.411 AC XY: 275534 AN XY: 670286

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.403

GnomAD4 genome AF: 0.330 AC: 50157 AN: 152026 Hom.: 9923 Cov.: 32 AF XY: 0.331 AC XY: 24559 AN XY: 74290

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.347

Alfa AF: 0.408 Hom.: 13390

Bravo AF: 0.305

Asia WGS AF: 0.277 AC: 966 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	-0.39
Cadd	Benign	17
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10835210; hg19: chr11-27695910; COSMIC: COSV59235355;