chr11-27699390-C-T

Position:

• chr11-27699390-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000395986.6(BDNF):​c.16G>A​(p.Glu6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 1,614,100 control chromosomes in the GnomAD database, including 2,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (130 hom., cov: 31)
  • Exomes 𝑓: 0.049 (2042 hom.)
• Consequence: BDNF ENST00000395986.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.310

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022384524).
• BP6: Variant 11-27699390-C-T is Benign according to our data. Variant chr11-27699390-C-T is described in ClinVar as [Benign]. Clinvar id is 162789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-27699390-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-22+774G>A		intron_variant		ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-22+774G>A		intron_variant		1	NM_001709.5	ENSP00000349084	P4
	ENST00000530663.1	n.148-2868G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5257 AN: 152144 Hom.: 130 Cov.: 31

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0393

GnomAD3 exomes AF: 0.0355 AC: 8852 AN: 249568 Hom.: 200 AF XY: 0.0357 AC XY: 4838 AN XY: 135404

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0161

Gnomad FIN exome AF: 0.0296

Gnomad NFE exome AF: 0.0536

Gnomad OTH exome AF: 0.0472

GnomAD4 exome AF: 0.0494 AC: 72199 AN: 1461838 Hom.: 2042 Cov.: 31 AF XY: 0.0482 AC XY: 35070 AN XY: 727220

Gnomad4 AFR exome AF: 0.00950

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.0577

Gnomad4 OTH exome AF: 0.0425

GnomAD4 genome AF: 0.0345 AC: 5259 AN: 152262 Hom.: 130 Cov.: 31 AF XY: 0.0321 AC XY: 2391 AN XY: 74452

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0543

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0490 Hom.: 357

Bravo AF: 0.0351

TwinsUK AF: 0.0558 AC: 207

ALSPAC AF: 0.0519 AC: 200

ESP6500AA AF: 0.0124 AC: 47

ESP6500EA AF: 0.0474 AC: 390

ExAC AF: 0.0357 AC: 4315

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.0529

EpiControl AF: 0.0504

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Glu6Lys in exon 1I of BDNF: This variant is not expected to have clinical signif icance because it has been identified in 4.7% (390/8232) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs66866077). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.9
DANN	Benign	0.88
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		0.94	P
Vest4		0.048
ClinPred		0.030	T
GERP RS		0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs66866077; hg19: chr11-27720937;