rs16917237

Variant names:

• chr11-27680836-G-T
• rs16917237
• NM_001709.5:c.-22+19328C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001709.5(BDNF):​c.-22+19328C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,116 control chromosomes in the GnomAD database, including 2,896 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 0.17 (2896 hom., cov: 32)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 62 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+19328C>A		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+19328C>A		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-22+18647C>A		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25315 AN: 151996 Hom.: 2898 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.166 AC: 25313 AN: 152116 Hom.: 2896 Cov.: 32 AF XY: 0.168 AC XY: 12513 AN XY: 74362

African (AFR) AF: 0.0410 AC: 1705 AN: 41538

American (AMR) AF: 0.172 AC: 2621 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 903 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2428 AN: 5150

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4818

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10586

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13911 AN: 67958

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.170 Hom.: 475

Bravo AF: 0.164

Asia WGS AF: 0.298 AC: 1033 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16917237; hg19: chr11-27702383;