NM_001709.5:c.-21-15778G>T

Variant names:

• chr11-27674363-C-A
• rs10835210
• NM_001709.5:c.-21-15778G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18
• Publications: 66 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 -18 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 VariationId is 1276343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 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.-21-15778G>T		intron	N/A	NP_001700.2
	BDNF	NM_001143810.2		c.-58-21G>T		intron	N/A	NP_001137282.1
	BDNF	NM_001143809.2		c.67-15778G>T		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.-21-15778G>T		intron	N/A	ENSP00000349084.4
	BDNF	ENST00000438929.5	TSL:1	c.-58-21G>T		intron	N/A	ENSP00000414303.1
	BDNF	ENST00000395986.6	TSL:1	c.25-15778G>T		intron	N/A	ENSP00000379309.2

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

African (AFR) AF: 0.109 AC: 3330 AN: 30650

American (AMR) AF: 0.265 AC: 8870 AN: 33470

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 11384 AN: 23254

East Asian (EAS) AF: 0.322 AC: 11431 AN: 35460

South Asian (SAS) AF: 0.289 AC: 21303 AN: 73622

European-Finnish (FIN) AF: 0.470 AC: 21445 AN: 45582

Middle Eastern (MID) AF: 0.442 AC: 1724 AN: 3904

European-Non Finnish (NFE) AF: 0.433 AC: 460957 AN: 1063808

Other (OTH) AF: 0.403 AC: 22743 AN: 56462

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

African (AFR) AF: 0.122 AC: 5043 AN: 41502

American (AMR) AF: 0.291 AC: 4444 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1421 AN: 5150

South Asian (SAS) AF: 0.284 AC: 1365 AN: 4804

European-Finnish (FIN) AF: 0.473 AC: 4993 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29959 AN: 67972

Other (OTH) AF: 0.347 AC: 732 AN: 2112

Alfa AF: 0.397 Hom.: 37173

Bravo AF: 0.305

Asia WGS AF: 0.277 AC: 966 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		1.2
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

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