rs11030121

Variant names:

• chr11-27714660-C-T
• rs11030121
• ENST00000314915.6:c.3+6752G>A

Variant summary

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

The ENST00000314915.6(BDNF):​c.3+6752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,720 control chromosomes in the GnomAD database, including 9,263 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 0.34 (9263 hom., cov: 32)
• Consequence: BDNF ENST00000314915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 20 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]

ENSG00000255496 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_170731.5	c.3+6752G>A		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+5984G>A		intron_variant	Intron 1 of 1		NP_001137277.1
BDNF	NM_001143806.1	c.-22+5769G>A		intron_variant	Intron 1 of 1		NP_001137278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000314915.6	c.3+6752G>A		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+5769G>A		intron_variant	Intron 1 of 1	1		ENSP00000379302.3
BDNF	ENST00000395981.7	c.-22+5686G>A		intron_variant	Intron 1 of 1	1		ENSP00000379305.3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51079 AN: 151602 Hom.: 9224 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.337 AC: 51169 AN: 151720 Hom.: 9263 Cov.: 32 AF XY: 0.335 AC XY: 24815 AN XY: 74100

African (AFR) AF: 0.459 AC: 18987 AN: 41358

American (AMR) AF: 0.271 AC: 4128 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3472

East Asian (EAS) AF: 0.0837 AC: 431 AN: 5150

South Asian (SAS) AF: 0.363 AC: 1739 AN: 4794

European-Finnish (FIN) AF: 0.349 AC: 3670 AN: 10506

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20607 AN: 67882

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.329 Hom.: 2677

Bravo AF: 0.335

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.31
PhyloP100		-0.22
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: rs11030121; hg19: chr11-27736207;