rs7934165

Variant names:

• chr11-27710436-G-A
• rs7934165
• ENST00000314915.6:c.3+10976C>T

Variant summary

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

The ENST00000314915.6(BDNF):​c.3+10976C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,988 control chromosomes in the GnomAD database, including 18,106 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 0.49 (18106 hom., cov: 32)
• Consequence: BDNF ENST00000314915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 51 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_170731.5	c.3+10976C>T		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+10208C>T		intron_variant	Intron 1 of 1		NP_001137277.1
BDNF	NM_001143806.1	c.-22+9993C>T		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+10976C>T		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+9993C>T		intron_variant	Intron 1 of 1	1		ENSP00000379302.3
BDNF	ENST00000395981.7	c.-22+9910C>T		intron_variant	Intron 1 of 1	1		ENSP00000379305.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73687 AN: 151870 Hom.: 18102 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.485 AC: 73716 AN: 151988 Hom.: 18106 Cov.: 32 AF XY: 0.485 AC XY: 36067 AN XY: 74296

African (AFR) AF: 0.478 AC: 19820 AN: 41454

American (AMR) AF: 0.551 AC: 8423 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2306 AN: 5166

South Asian (SAS) AF: 0.333 AC: 1606 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5184 AN: 10562

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33005 AN: 67918

Other (OTH) AF: 0.487 AC: 1029 AN: 2114

Alfa AF: 0.483 Hom.: 80515

Bravo AF: 0.489

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.50
PhyloP100		1.8
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: rs7934165; hg19: chr11-27731983;