chr11-27722009-G-T

Variant names:

• chr11-27722009-G-T
• rs28383487
• ENST00000314915.6:c.-595C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_170731.5(BDNF):​c.-595C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,640 control chromosomes in the GnomAD database, including 45 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 0.015 (45 hom., cov: 31)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: BDNF NM_170731.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661
• Publications: 11 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BS2: High AC in GnomAd4 at 2273 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170731.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_170731.5		c.-595C>A		5_prime_UTR	Exon 1 of 2	NP_733927.1	P23560-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000314915.6	TSL:1	c.-595C>A		5_prime_UTR	Exon 1 of 2	ENSP00000320002.6	P23560-2
	ENSG00000255496	ENST00000530663.1	TSL:1	n.148-25487C>A		intron	N/A
	ENSG00000309152	ENST00000839060.1		n.64+42G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2274 AN: 151910 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0114 AC: 7 AN: 616 Hom.: 0 Cov.: 0 AF XY: 0.0155 AC XY: 5 AN XY: 322

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.0625 AC: 1 AN: 16

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0130 AC: 6 AN: 462

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome AF: 0.0150 AC: 2273 AN: 152024 Hom.: 45 Cov.: 31 AF XY: 0.0163 AC XY: 1209 AN XY: 74270

African (AFR) AF: 0.00260 AC: 108 AN: 41464

American (AMR) AF: 0.00851 AC: 130 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4816

European-Finnish (FIN) AF: 0.0651 AC: 686 AN: 10532

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0156 AC: 1061 AN: 67996

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0129 Hom.: 13

Bravo AF: 0.0107

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		0.66
PromoterAI		-0.012	Neutral
Mutation Taster		=298/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs28383487; hg19: chr11-27743556;