2-119367482-C-T

Variant names:

• chr2-119367482-C-T
• rs3731607
• ENST00000627305.2:c.146C>T

Variant summary

Our verdict is Benign. The variant received -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. 10/15 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
• Publications: 17 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 (MetaRNN=0.0037445128).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000627305.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	NM_001079862.4	MANE Select	c.9+422C>T		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.146C>T	p.Ala49Val	missense	Exon 1 of 4	NP_001171488.1
	DBI	NM_001178041.4		c.89C>T	p.Ala30Val	missense	Exon 2 of 5	NP_001171512.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000627305.2	TSL:1	c.146C>T	p.Ala49Val	missense	Exon 1 of 4	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.89C>T	p.Ala30Val	missense	Exon 2 of 5	ENSP00000486281.1
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.9+422C>T		intron	N/A	ENSP00000348116.3

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

GnomAD2 exomes AF: 0.174 AC: 40798 AN: 233826 AF XY: 0.173

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 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

African (AFR) AF: 0.128 AC: 4233 AN: 33178

American (AMR) AF: 0.156 AC: 6776 AN: 43460

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3402 AN: 25150

East Asian (EAS) AF: 0.244 AC: 9570 AN: 39222

South Asian (SAS) AF: 0.127 AC: 10755 AN: 84662

European-Finnish (FIN) AF: 0.170 AC: 8895 AN: 52418

Middle Eastern (MID) AF: 0.0813 AC: 462 AN: 5682

European-Non Finnish (NFE) AF: 0.207 AC: 227766 AN: 1098520

Other (OTH) AF: 0.178 AC: 10536 AN: 59350

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

African (AFR) AF: 0.136 AC: 5623 AN: 41488

American (AMR) AF: 0.164 AC: 2505 AN: 15278

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

East Asian (EAS) AF: 0.227 AC: 1167 AN: 5132

South Asian (SAS) AF: 0.137 AC: 663 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1647 AN: 10588

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

European-Non Finnish (NFE) AF: 0.202 AC: 13752 AN: 67916

Other (OTH) AF: 0.154 AC: 325 AN: 2108

Alfa AF: 0.190 Hom.: 5165

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
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
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.37
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.024	D
Vest4		0.18
ClinPred		0.0082	T
GERP RS		0.67
PromoterAI		-0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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