ENST00000532997.5:c.-56C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The ENST00000532997.5(BDNF):​c.-56C>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 0.000006 in 833,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000060 (0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532997.5. 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_001143807.2		c.-56C>A		5_prime_UTR	Exon 1 of 2	NP_001137279.1	A0A0E3SU01
	BDNF	NM_170731.5		c.3+1867C>A		intron	N/A	NP_733927.1	P23560-2
	BDNF	NM_001143805.1		c.-22+1099C>A		intron	N/A	NP_001137277.1	P23560-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000532997.5	TSL:1	c.-56C>A		5_prime_UTR	Exon 1 of 2	ENSP00000435805.1	P23560-1
	BDNF	ENST00000314915.6	TSL:1	c.3+1867C>A		intron	N/A	ENSP00000320002.6	P23560-2
	BDNF	ENST00000395978.7	TSL:1	c.-22+884C>A		intron	N/A	ENSP00000379302.3	P23560-1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000600 AC: 5 AN: 833232 Hom.: 0 Cov.: 31 AF XY: 0.00000780 AC XY: 3 AN XY: 384808

African (AFR) AF: 0.000190 AC: 3 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5154

East Asian (EAS) AF: 0.00 AC: 0 AN: 3632

South Asian (SAS) AF: 0.00 AC: 0 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.000616 AC: 1 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 762004

Other (OTH) AF: 0.0000366 AC: 1 AN: 27312

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 1015

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		0.91
PromoterAI		0.0019	Neutral

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;