11-27655494-C-T

Variant names:

• chr11-27655494-C-T
• rs7124442
• NM_001709.5:c.*2327G>A

Variant summary

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

The NM_001709.5(BDNF):​c.*2327G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,022 control chromosomes in the GnomAD database, including 33,832 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 0.66 (33831 hom., cov: 32)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: BDNF NM_001709.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 116 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]

BDNF-AS (HGNC:20608): (BDNF antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001709.5. 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_001709.5	MANE Select	c.*2327G>A		3_prime_UTR	Exon 2 of 2	NP_001700.2
	BDNF	NM_001143810.2		c.*2327G>A		3_prime_UTR	Exon 3 of 3	NP_001137282.1	P23560-4
	BDNF	NM_001143809.2		c.*2327G>A		3_prime_UTR	Exon 2 of 2	NP_001137281.1	P23560-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.*2327G>A		3_prime_UTR	Exon 2 of 2	ENSP00000349084.4	P23560-1
	BDNF	ENST00000438929.5	TSL:1	c.*2327G>A		3_prime_UTR	Exon 3 of 3	ENSP00000414303.1	P23560-4
	BDNF	ENST00000395986.6	TSL:1	c.*2327G>A		3_prime_UTR	Exon 2 of 2	ENSP00000379309.2	P23560-3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100442 AN: 151896 Hom.: 33824 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.661 AC: 100467 AN: 152014 Hom.: 33831 Cov.: 32 AF XY: 0.664 AC XY: 49304 AN XY: 74302

African (AFR) AF: 0.543 AC: 22519 AN: 41434

American (AMR) AF: 0.729 AC: 11140 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2835 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4743 AN: 5178

South Asian (SAS) AF: 0.618 AC: 2974 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6871 AN: 10538

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 47012 AN: 67986

Other (OTH) AF: 0.682 AC: 1438 AN: 2110

Alfa AF: 0.686 Hom.: 93714

Bravo AF: 0.663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.4
DANN	Benign	0.53
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7124442; hg19: chr11-27677041;