2-119367453-A-G

Variant names:

• chr2-119367453-A-G
• rs2084202
• ENST00000627305.2:c.117A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001178017.3(DBI):​c.117A>G​(p.Arg39Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,567,592 control chromosomes in the GnomAD database, including 564,833 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 0.87 (58376 hom., cov: 31)
  • Exomes 𝑓: 0.85 (506457 hom.)
• Consequence: DBI NM_001178017.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.288242E-7).
• BP7: Synonymous conserved (PhyloP=-0.501 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178017.3. 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.9+393A>G		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.117A>G	p.Arg39Arg	synonymous	Exon 1 of 4	NP_001171488.1
	DBI	NM_001178041.4		c.60A>G	p.Arg20Arg	synonymous	Exon 2 of 5	NP_001171512.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000627305.2	TSL:1	c.117A>G	p.Arg39Arg	synonymous	Exon 1 of 4	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.60A>G	p.Arg20Arg	synonymous	Exon 2 of 5	ENSP00000486281.1
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.9+393A>G		intron	N/A	ENSP00000348116.3

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132874 AN: 151960 Hom.: 58318 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.880

GnomAD2 exomes AF: 0.842 AC: 167267 AN: 198740 AF XY: 0.845

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.737

Gnomad ASJ exome AF: 0.879

Gnomad EAS exome AF: 0.902

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.842

Gnomad OTH exome AF: 0.839

GnomAD4 exome AF: 0.845 AC: 1196590 AN: 1415514 Hom.: 506457 Cov.: 69 AF XY: 0.846 AC XY: 591147 AN XY: 698674

African (AFR) AF: 0.957 AC: 31243 AN: 32632

American (AMR) AF: 0.749 AC: 29715 AN: 39664

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 21173 AN: 24034

East Asian (EAS) AF: 0.922 AC: 35335 AN: 38334

South Asian (SAS) AF: 0.869 AC: 70609 AN: 81244

European-Finnish (FIN) AF: 0.826 AC: 40902 AN: 49544

Middle Eastern (MID) AF: 0.871 AC: 4885 AN: 5610

European-Non Finnish (NFE) AF: 0.840 AC: 912803 AN: 1086092

Other (OTH) AF: 0.855 AC: 49925 AN: 58360

GnomAD4 genome AF: 0.874 AC: 132987 AN: 152078 Hom.: 58376 Cov.: 31 AF XY: 0.873 AC XY: 64856 AN XY: 74298

African (AFR) AF: 0.954 AC: 39629 AN: 41520

American (AMR) AF: 0.821 AC: 12548 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3064 AN: 3472

East Asian (EAS) AF: 0.895 AC: 4603 AN: 5144

South Asian (SAS) AF: 0.872 AC: 4204 AN: 4820

European-Finnish (FIN) AF: 0.824 AC: 8708 AN: 10570

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57301 AN: 67952

Other (OTH) AF: 0.881 AC: 1856 AN: 2106

Alfa AF: 0.881 Hom.: 20814

Bravo AF: 0.875

TwinsUK AF: 0.838 AC: 3108

ALSPAC AF: 0.846 AC: 3260

ExAC AF: 0.837 AC: 99909

Asia WGS AF: 0.874 AC: 3039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.49
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	8.3e-7	T
PhyloP100		-0.50
Sift4G	Benign	0.22	T
Vest4		0.065
GERP RS		-3.8
PromoterAI		-0.0068	Neutral
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: rs2084202; hg19: chr2-120125029; COSMIC: COSV58347243; COSMIC: COSV58347243;