2-119367482-C-T

Position:

• chr2-119367482-C-T

Variant summary

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

The ENST00000627305.2(DBI):​c.146C>T​(p.Ala49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,593,650 control chromosomes in the GnomAD database, including 30,778 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict 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 (2451 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28327 hom.)
• Consequence: DBI ENST00000627305.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=0.0037445128).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBI	NM_001079862.4	c.9+422C>T		intron_variant		ENST00000355857.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBI	ENST00000355857.8	c.9+422C>T		intron_variant		1	NM_001079862.4	P4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26321 AN: 151890 Hom.: 2450 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.227

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

GnomAD3 exomes AF: 0.174 AC: 40798 AN: 233826 Hom.: 3689 AF XY: 0.173 AC XY: 22058 AN XY: 127150

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.196 AC: 282395 AN: 1441642 Hom.: 28327 Cov.: 48 AF XY: 0.193 AC XY: 137799 AN XY: 713960

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.173 AC: 26337 AN: 152008 Hom.: 2451 Cov.: 32 AF XY: 0.171 AC XY: 12695 AN XY: 74288

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.154

Alfa AF: 0.195 Hom.: 3695

Bravo AF: 0.172

TwinsUK AF: 0.192 AC: 711

ALSPAC AF: 0.202 AC: 779

ExAC AF: 0.172 AC: 20796

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.8
DANN	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.58	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.024	D;D
Vest4		0.18
ClinPred		0.0082	T
GERP RS		0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.038

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3731607; hg19: chr2-120125058; COSMIC: COSV58345439; COSMIC: COSV58345439;