ENST00000439476.6:c.-831G>C

Variant names:

• chr11-27659629-C-G
• rs28722151
• ENST00000439476.6:c.-831G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000439476.6(BDNF):​c.-831G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,392 control chromosomes in the GnomAD database, including 10,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10474 hom., cov: 29)
  • Exomes 𝑓: 0.43 (77140 hom.)
  • Failed GnomAD Quality Control
• Consequence: BDNF ENST00000439476.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-27659629-C-G is Benign according to our data. Variant chr11-27659629-C-G is described in ClinVar as Benign. ClinVar VariationId is 1258199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-1044G>C		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-1044G>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-1044G>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52509 AN: 151276 Hom.: 10476 Cov.: 29

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.362

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.432 AC: 359240 AN: 831212 Hom.: 77140 Cov.: 36 AF XY: 0.432 AC XY: 166012 AN XY: 384334

African (AFR) AF: 0.153 AC: 2306 AN: 15028

American (AMR) AF: 0.296 AC: 284 AN: 958

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 2660 AN: 5084

East Asian (EAS) AF: 0.275 AC: 977 AN: 3556

South Asian (SAS) AF: 0.309 AC: 4995 AN: 16190

European-Finnish (FIN) AF: 0.478 AC: 7013 AN: 14678

Middle Eastern (MID) AF: 0.479 AC: 761 AN: 1588

European-Non Finnish (NFE) AF: 0.440 AC: 328734 AN: 747264

Other (OTH) AF: 0.428 AC: 11510 AN: 26866

GnomAD4 genome AF: 0.347 AC: 52508 AN: 151392 Hom.: 10474 Cov.: 29 AF XY: 0.347 AC XY: 25675 AN XY: 73962

African (AFR) AF: 0.161 AC: 6624 AN: 41120

American (AMR) AF: 0.303 AC: 4608 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1787 AN: 3464

East Asian (EAS) AF: 0.277 AC: 1410 AN: 5084

South Asian (SAS) AF: 0.305 AC: 1461 AN: 4792

European-Finnish (FIN) AF: 0.476 AC: 4995 AN: 10504

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30350 AN: 67916

Other (OTH) AF: 0.363 AC: 762 AN: 2100

Alfa AF: 0.318 Hom.: 674

Bravo AF: 0.325

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-0.34
PromoterAI		0.0076	Neutral
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: rs28722151; hg19: chr11-27681176;