2-119368113-A-T

Variant names:

• chr2-119368113-A-T
• rs8192503
• NM_001079862.4:c.10-75A>T

Variant summary

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

The NM_001079862.4(DBI):​c.10-75A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,499,806 control chromosomes in the GnomAD database, including 29,122 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 0.17 (2475 hom., cov: 33)
  • Exomes 𝑓: 0.20 (26647 hom.)
• Consequence: DBI NM_001079862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBI	NM_001079862.4	c.10-75A>T		intron_variant	Intron 1 of 3	ENST00000355857.8	NP_001073331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBI	ENST00000355857.8	c.10-75A>T		intron_variant	Intron 1 of 3	1	NM_001079862.4	ENSP00000348116.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26331 AN: 152066 Hom.: 2474 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.196 AC: 263593 AN: 1347622 Hom.: 26647 Cov.: 21 AF XY: 0.193 AC XY: 130434 AN XY: 676464

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.173 AC: 26347 AN: 152184 Hom.: 2475 Cov.: 33 AF XY: 0.171 AC XY: 12715 AN XY: 74394

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.154

Alfa AF: 0.179 Hom.: 333

Bravo AF: 0.171

Asia WGS AF: 0.163 AC: 567 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	3.4
DANN	Benign	0.54

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: rs8192503; hg19: chr2-120125689; COSMIC: COSV58346962; COSMIC: COSV58346962;