2-119368360-T-C

Variant names:

• chr2-119368360-T-C
• rs2244135
• NM_001079862.4:c.127+55T>C

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+55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,343,640 control chromosomes in the GnomAD database, including 474,708 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 0.86 (57126 hom., cov: 32)
  • Exomes 𝑓: 0.84 (417582 hom.)
• Consequence: DBI NM_001079862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	NM_001079862.4	MANE Select	c.127+55T>C		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.310+55T>C		intron	N/A	NP_001171488.1
	DBI	NM_001178041.4		c.253+55T>C		intron	N/A	NP_001171512.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.127+55T>C		intron	N/A	ENSP00000348116.3
	DBI	ENST00000627305.2	TSL:1	c.310+55T>C		intron	N/A	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.253+55T>C		intron	N/A	ENSP00000486281.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131521 AN: 152138 Hom.: 57069 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.836 AC: 996202 AN: 1191384 Hom.: 417582 Cov.: 16 AF XY: 0.836 AC XY: 506315 AN XY: 605702

African (AFR) AF: 0.946 AC: 26710 AN: 28228

American (AMR) AF: 0.741 AC: 32799 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 21307 AN: 24280

East Asian (EAS) AF: 0.897 AC: 34466 AN: 38432

South Asian (SAS) AF: 0.825 AC: 66634 AN: 80770

European-Finnish (FIN) AF: 0.826 AC: 43288 AN: 52402

Middle Eastern (MID) AF: 0.844 AC: 4402 AN: 5218

European-Non Finnish (NFE) AF: 0.835 AC: 723191 AN: 866398

Other (OTH) AF: 0.845 AC: 43405 AN: 51388

GnomAD4 genome AF: 0.865 AC: 131633 AN: 152256 Hom.: 57126 Cov.: 32 AF XY: 0.862 AC XY: 64179 AN XY: 74446

African (AFR) AF: 0.945 AC: 39268 AN: 41542

American (AMR) AF: 0.809 AC: 12376 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3050 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4497 AN: 5178

South Asian (SAS) AF: 0.825 AC: 3985 AN: 4830

European-Finnish (FIN) AF: 0.823 AC: 8721 AN: 10600

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56829 AN: 68018

Other (OTH) AF: 0.869 AC: 1835 AN: 2112

Alfa AF: 0.844 Hom.: 101497

Bravo AF: 0.865

Asia WGS AF: 0.841 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.9
DANN	Benign	0.59
PhyloP100		0.055
Mutation Taster		=8/92	disease causing

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: rs2244135; hg19: chr2-120125936;