11-27719545-G-A

Variant names:

• chr11-27719545-G-A
• rs2883187
• ENST00000532997.5:c.-56C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000532997.5(BDNF):​c.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 984,812 control chromosomes in the GnomAD database, including 104,789 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 0.41 (13988 hom., cov: 29)
  • Exomes 𝑓: 0.46 (90801 hom.)
• Consequence: BDNF ENST00000532997.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 23 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001143807.2	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2		NP_001137279.1
BDNF	NM_170731.5	c.3+1867C>T		intron_variant	Intron 1 of 1		NP_733927.1
BDNF	NM_001143805.1	c.-22+1099C>T		intron_variant	Intron 1 of 1		NP_001137277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000532997.5	c.-56C>T		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000435805.1
BDNF	ENST00000314915.6	c.3+1867C>T		intron_variant	Intron 1 of 1	1		ENSP00000320002.6
BDNF	ENST00000395978.7	c.-22+884C>T		intron_variant	Intron 1 of 1	1		ENSP00000379302.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61801 AN: 151492 Hom.: 13987 Cov.: 29

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.464 AC: 386611 AN: 833200 Hom.: 90801 Cov.: 31 AF XY: 0.464 AC XY: 178628 AN XY: 384802

African (AFR) AF: 0.190 AC: 3002 AN: 15786

American (AMR) AF: 0.575 AC: 566 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 2668 AN: 5154

East Asian (EAS) AF: 0.456 AC: 1656 AN: 3632

South Asian (SAS) AF: 0.332 AC: 5459 AN: 16460

European-Finnish (FIN) AF: 0.460 AC: 127 AN: 276

Middle Eastern (MID) AF: 0.490 AC: 795 AN: 1624

European-Non Finnish (NFE) AF: 0.472 AC: 359750 AN: 761972

Other (OTH) AF: 0.461 AC: 12588 AN: 27312

GnomAD4 genome AF: 0.408 AC: 61811 AN: 151612 Hom.: 13988 Cov.: 29 AF XY: 0.411 AC XY: 30441 AN XY: 74060

African (AFR) AF: 0.211 AC: 8712 AN: 41366

American (AMR) AF: 0.527 AC: 8026 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1779 AN: 3466

East Asian (EAS) AF: 0.444 AC: 2268 AN: 5108

South Asian (SAS) AF: 0.333 AC: 1594 AN: 4792

European-Finnish (FIN) AF: 0.490 AC: 5137 AN: 10494

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32832 AN: 67838

Other (OTH) AF: 0.430 AC: 905 AN: 2106

Alfa AF: 0.335 Hom.: 1015

Bravo AF: 0.403

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		0.91
PromoterAI		0.0028	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2883187; hg19: chr11-27741092;