Variant 2-119372265-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001079862.4(DBI):c.211A>G(p.Met71Val) variant causes a missense change. The variant allele was found at a frequency of 0.0337 in 1,612,796 control chromosomes in the GnomAD database, including 1,114 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.023 ( 66 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1048 hom. )

Consequence

DBI
NM_001079862.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

DBI (HGNC:2690): (diazepam binding inhibitor, acyl-CoA binding protein) This gene encodes diazepam binding inhibitor, a protein that is regulated by hormones and is involved in lipid metabolism and the displacement of beta-carbolines and benzodiazepines, which modulate signal transduction at type A gamma-aminobutyric acid receptors located in brain synapses. The protein is conserved from yeast to mammals, with the most highly conserved domain consisting of seven contiguous residues that constitute the hydrophobic binding site for medium- and long-chain acyl-Coenzyme A esters. Diazepam binding inhibitor is also known to mediate the feedback regulation of pancreatic secretion and the postprandial release of cholecystokinin, in addition to its role as a mediator in corticotropin-dependent adrenal steroidogenesis. Three pseudogenes located on chromosomes 6, 8 and 16 have been identified. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DBI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006292224).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0234 (3560/152344) while in subpopulation NFE AF= 0.0377 (2564/68020). AF 95% confidence interval is 0.0365. There are 66 homozygotes in gnomad4. There are 1658 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 66 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBI	NM_001079862.4 link	c.211A>G	p.Met71Val	missense_variant	4/4	ENST00000355857.8	NP_001073331.1	P07108-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBI	ENST00000355857.8 link	c.211A>G	p.Met71Val	missense_variant	4/4	1	NM_001079862.4	ENSP00000348116.3		P07108-1

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3560

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0377

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0247

AC:

6211

AN:

251394

Hom.:

115

AF XY:

0.0246

AC XY:

3337

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00578

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0451

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00728

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0347

AC:

50742

AN:

1460452

Hom.:

1048

Cov.:

AF XY:

0.0339

AC XY:

24657

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.00577

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0475

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00717

Gnomad4 FIN exome

AF:

0.0237

Gnomad4 NFE exome

AF:

0.0405

Gnomad4 OTH exome

AF:

0.0281

GnomAD4 genome

AF:

0.0234

AC:

3560

AN:

152344

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00630

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0336

Hom.:

260

Bravo

AF:

0.0222

TwinsUK

AF:

0.0394

AC:

146

ALSPAC

AF:

0.0436

AC:

168

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0362

AC:

311

ExAC

AF:

0.0250

AC:

3040

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0332

EpiControl

AF:

0.0362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

T;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D;.;D;.;D;D

MetaRNN

Benign

0.0063

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;D;.;.;D;.;D;.;D

REVEL

Benign

0.14

Sift

Benign

0.11

T;T;.;.;T;.;T;.;T

Sift4G

Benign

0.14

T;T;T;T;T;D;T;D;T

Polyphen

0.010

B;.;B;.;.;.;.;.;B

Vest4

0.22

MPC

0.46

ClinPred

0.029

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over