2-119368334-C-A

Variant names:

• chr2-119368334-C-A
• rs2276596
• NM_001079862.4:c.127+29C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079862.4(DBI):​c.127+29C>A 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 1,544,756 control chromosomes in the GnomAD database, including 29,815 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 (2471 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27344 hom.)
• Consequence: DBI NM_001079862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	NM_001079862.4	MANE Select	c.127+29C>A		intron	N/A	NP_001073331.1	P07108-1
	DBI	NM_001178017.3		c.310+29C>A		intron	N/A	NP_001171488.1	P07108-5
	DBI	NM_001178041.4		c.253+29C>A		intron	N/A	NP_001171512.1	P07108-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.127+29C>A		intron	N/A	ENSP00000348116.3	P07108-1
	DBI	ENST00000627305.2	TSL:1	c.310+29C>A		intron	N/A	ENSP00000486361.1	P07108-5
	DBI	ENST00000627093.2	TSL:1	c.253+29C>A		intron	N/A	ENSP00000486281.1	P07108-4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26344 AN: 152118 Hom.: 2470 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.175 AC: 44008 AN: 250776 AF XY: 0.175

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.195 AC: 271239 AN: 1392520 Hom.: 27344 Cov.: 22 AF XY: 0.192 AC XY: 133797 AN XY: 696528

African (AFR) AF: 0.128 AC: 4108 AN: 32128

American (AMR) AF: 0.156 AC: 6968 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3494 AN: 25706

East Asian (EAS) AF: 0.245 AC: 9638 AN: 39414

South Asian (SAS) AF: 0.127 AC: 10805 AN: 84916

European-Finnish (FIN) AF: 0.170 AC: 9046 AN: 53234

Middle Eastern (MID) AF: 0.0814 AC: 459 AN: 5636

European-Non Finnish (NFE) AF: 0.206 AC: 216472 AN: 1048794

Other (OTH) AF: 0.176 AC: 10249 AN: 58076

GnomAD4 genome AF: 0.173 AC: 26359 AN: 152236 Hom.: 2471 Cov.: 32 AF XY: 0.171 AC XY: 12720 AN XY: 74438

African (AFR) AF: 0.136 AC: 5661 AN: 41538

American (AMR) AF: 0.158 AC: 2417 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5174

South Asian (SAS) AF: 0.137 AC: 662 AN: 4826

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10594

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13808 AN: 68020

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.177 Hom.: 483

Bravo AF: 0.171

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.46
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2276596; hg19: chr2-120125910; COSMIC: COSV58346744; COSMIC: COSV58346744;