2-119372265-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.023 (66 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1048 hom.)
• Consequence: DBI NM_001079862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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]

ACMG classification

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 GnomAd at 66 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBI	ENST00000355857.8	c.211A>G	p.Met71Val	missense_variant	4/4	1	NM_001079862.4	P4

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3560 AN: 152226 Hom.: 66 Cov.: 33

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

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.: 29 AF XY: 0.0339 AC XY: 24657 AN XY: 726664

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.: 66 Cov.: 33 AF XY: 0.0223 AC XY: 1658 AN XY: 74504

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: 24

ESP6500EA AF: 0.0362 AC: 311

ExAC AF: 0.0250 AC: 3040

Asia WGS AF: 0.00404 AC: 14 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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.38	T;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
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	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.39	T
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	T
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

Other links and lift over

dbSNP: rs8192506; hg19: chr2-120129841; COSMIC: COSV61055619; COSMIC: COSV61055619;