2-119368360-T-C

Position:

• chr2-119368360-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079862.4(DBI):​c.127+55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,343,640 control chromosomes in the GnomAD database, including 474,708 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 0.86 (57126 hom., cov: 32)
  • Exomes 𝑓: 0.84 (417582 hom.)
• Consequence: DBI NM_001079862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBI	NM_001079862.4	c.127+55T>C		intron_variant		ENST00000355857.8	NP_001073331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBI	ENST00000355857.8	c.127+55T>C		intron_variant		1	NM_001079862.4	ENSP00000348116.3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131521 AN: 152138 Hom.: 57069 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.836 AC: 996202 AN: 1191384 Hom.: 417582 Cov.: 16 AF XY: 0.836 AC XY: 506315 AN XY: 605702

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.825

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.865 AC: 131633 AN: 152256 Hom.: 57126 Cov.: 32 AF XY: 0.862 AC XY: 64179 AN XY: 74446

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.869

Alfa AF: 0.841 Hom.: 72941

Bravo AF: 0.865

Asia WGS AF: 0.841 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.9
DANN	Benign	0.59

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: rs2244135; hg19: chr2-120125936;