chr11-27658648-A-G

Variant names:

• chr11-27658648-A-G
• rs3750934
• NM_001709.5:c.-21-63T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001709.5(BDNF):​c.-21-63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,613,506 control chromosomes in the GnomAD database, including 56 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 0.0039 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (44 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00394 (601/152350) while in subpopulation EAS AF = 0.0245 (127/5184). AF 95% confidence interval is 0.021. There are 12 homozygotes in GnomAd4. There are 402 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 601 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	NM_001709.5	MANE Select	c.-21-63T>C		intron	N/A	NP_001700.2
	BDNF	NM_170735.6		c.-84T>C		5_prime_UTR	Exon 1 of 1	NP_733931.1
	BDNF	NM_001143810.2		c.226-63T>C		intron	N/A	NP_001137282.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDNF	ENST00000356660.9	TSL:1 MANE Select	c.-21-63T>C		intron	N/A	ENSP00000349084.4
	BDNF	ENST00000438929.5	TSL:1	c.226-63T>C		intron	N/A	ENSP00000414303.1
	BDNF	ENST00000395986.6	TSL:1	c.25-63T>C		intron	N/A	ENSP00000379309.2

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 600 AN: 152232 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00218 AC: 3182 AN: 1461156 Hom.: 44 Cov.: 33 AF XY: 0.00208 AC XY: 1514 AN XY: 726844

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000448 AC: 2 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0193 AC: 765 AN: 39696

South Asian (SAS) AF: 0.000570 AC: 49 AN: 86010

European-Finnish (FIN) AF: 0.0355 AC: 1885 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000309 AC: 344 AN: 1111876

Other (OTH) AF: 0.00225 AC: 136 AN: 60390

GnomAD4 genome AF: 0.00394 AC: 601 AN: 152350 Hom.: 12 Cov.: 32 AF XY: 0.00540 AC XY: 402 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.0369 AC: 392 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00117

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.42
PhyloP100		-1.5
Mutation Taster		=299/1	polymorphism

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: rs3750934; hg19: chr11-27680195;