2-119372265-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

23 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 66 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBI	NM_001079862.4	MANE Select	c.211A>G	p.Met71Val	missense	Exon 4 of 4	NP_001073331.1	P07108-1
DBI	NM_001178017.3		c.394A>G	p.Met132Val	missense	Exon 4 of 4	NP_001171488.1	P07108-5
DBI	NM_001178041.4		c.337A>G	p.Met113Val	missense	Exon 5 of 5	NP_001171512.1	P07108-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBI	ENST00000355857.8	TSL:1 MANE Select	c.211A>G	p.Met71Val	missense	Exon 4 of 4	ENSP00000348116.3	P07108-1
DBI	ENST00000627305.2	TSL:1	c.394A>G	p.Met132Val	missense	Exon 4 of 4	ENSP00000486361.1	P07108-5
DBI	ENST00000627093.2	TSL:1	c.337A>G	p.Met113Val	missense	Exon 5 of 5	ENSP00000486281.1	P07108-4

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

GnomAD2 exomes

AF:

0.0247

AC:

6211

AN:

251394

AF XY:

0.0246

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 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

African (AFR)

AF:

0.00577

AC:

193

AN:

33472

American (AMR)

AF:

0.0136

AC:

609

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0475

AC:

1242

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00717

AC:

618

AN:

86224

European-Finnish (FIN)

AF:

0.0237

AC:

1267

AN:

53368

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0405

AC:

45030

AN:

1110752

Other (OTH)

AF:

0.0281

AC:

1696

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

2200

4401

6601

8802

11002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1682

3364

5046

6728

8410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0234

AC:

3560

AN:

152344

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00630

AC:

262

AN:

41584

American (AMR)

AF:

0.0180

AC:

276

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0461

AC:

160

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0186

AC:

198

AN:

10628

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0377

AC:

2564

AN:

68020

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

166

332

498

664

830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0321

Hom.:

324

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.96

PhyloP100

3.8

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.14

Polyphen

0.010

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

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over