2-119367482-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000627305.2(DBI):​c.146C>G​(p.Ala49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09076825).

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>G		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.146C>G	p.Ala49Gly	missense	Exon 1 of 4	NP_001171488.1
	DBI	NM_001178041.4		c.89C>G	p.Ala30Gly	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>G	p.Ala49Gly	missense	Exon 1 of 4	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.89C>G	p.Ala30Gly	missense	Exon 2 of 5	ENSP00000486281.1
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.9+422C>G		intron	N/A	ENSP00000348116.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2 AN: 1442192 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 714294

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33190

American (AMR) AF: 0.00 AC: 0 AN: 43524

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 39242

South Asian (SAS) AF: 0.00 AC: 0 AN: 84688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098866

Other (OTH) AF: 0.00 AC: 0 AN: 59380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151944 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74192

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 5165

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.1
DANN	Benign	0.96
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.37
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.043	D
Vest4		0.21
MVP		0.16
ClinPred		0.090	T
GERP RS		0.67
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.042
Mutation Taster		=100/0	polymorphism

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;