11-27700731-G-T

Variant names:

• chr11-27700731-G-T
• rs61888800
• ENST00000530861.5:c.-77C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143812.2(BDNF):​c.-77C>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 0.234 in 1,184,476 control chromosomes in the GnomAD database, including 34,479 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 0.19 (3080 hom., cov: 32)
  • Exomes 𝑓: 0.24 (31399 hom.)
• Consequence: BDNF NM_001143812.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001143812.2	c.-77C>A		5_prime_UTR_variant	Exon 1 of 2		NP_001137284.1
BDNF	NM_001143810.2	c.-59+240C>A		intron_variant	Intron 1 of 2		NP_001137282.1
BDNF	NM_001143809.2	c.66+240C>A		intron_variant	Intron 1 of 1		NP_001137281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000530861.5	c.-77C>A		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000435564.1
BDNF	ENST00000438929.5	c.-59+240C>A		intron_variant	Intron 1 of 2	1		ENSP00000414303.1
BDNF	ENST00000314915.6	c.3+20681C>A		intron_variant	Intron 1 of 1	1		ENSP00000320002.6

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28222 AN: 151988 Hom.: 3080 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0105

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.241 AC: 248674 AN: 1032372 Hom.: 31399 Cov.: 32 AF XY: 0.236 AC XY: 116606 AN XY: 493910

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.00600

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.186 AC: 28227 AN: 152104 Hom.: 3080 Cov.: 32 AF XY: 0.181 AC XY: 13430 AN XY: 74358

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.193

Alfa AF: 0.145 Hom.: 334

Bravo AF: 0.181

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61888800; hg19: chr11-27722278;