rs8192501

chr2-119367739-G-Achr2-119367739-G-C

Variant summary

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

The ENST00000393103.2(DBI):c.-181G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,607,268 control chromosomes in the GnomAD database, including 793 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 0.021 (48 hom., cov: 32)
  • Exomes 𝑓: 0.028 (745 hom.)
• Consequence: DBI ENST00000393103.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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 (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0209 (3177/152258) while in subpopulation NFE AF= 0.0325 (2207/68006). AF 95% confidence interval is 0.0313. There are 48 homozygotes in gnomad4. There are 1444 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBI	NM_001079862.4	c.10-449G>A		intron_variant		ENST00000355857.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBI	ENST00000355857.8	c.10-449G>A		intron_variant		1	NM_001079862.4	P4

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3177 AN: 152140 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0281 AC: 40948 AN: 1455010 Hom.: 745 Cov.: 50 AF XY: 0.0278 AC XY: 20069 AN XY: 723060

Gnomad4 AFR exome AF: 0.00381

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00997

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0209 AC: 3177 AN: 152258 Hom.: 48 Cov.: 32 AF XY: 0.0194 AC XY: 1444 AN XY: 74444

Gnomad4 AFR AF: 0.00520

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.00706 Hom.: 3

Bravo AF: 0.0212

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.6
Dann	Benign	0.69

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: rs8192501; hg19: chr2-120125315; COSMIC: COSV58347655; COSMIC: COSV58347655;