2-119368113-A-T

Variant names:

• chr2-119368113-A-T
• rs8192503
• NM_001079862.4:c.10-75A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079862.4(DBI):​c.10-75A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,499,806 control chromosomes in the GnomAD database, including 29,122 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 0.17 (2475 hom., cov: 33)
  • Exomes 𝑓: 0.20 (26647 hom.)
• Consequence: DBI NM_001079862.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.218 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.10-75A>T		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.193-75A>T		intron	N/A	NP_001171488.1
	DBI	NM_001178041.4		c.136-75A>T		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.10-75A>T		intron	N/A	ENSP00000348116.3
	DBI	ENST00000627305.2	TSL:1	c.193-75A>T		intron	N/A	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.136-75A>T		intron	N/A	ENSP00000486281.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26331 AN: 152066 Hom.: 2474 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.196 AC: 263593 AN: 1347622 Hom.: 26647 Cov.: 21 AF XY: 0.193 AC XY: 130434 AN XY: 676464

African (AFR) AF: 0.127 AC: 3946 AN: 31100

American (AMR) AF: 0.157 AC: 6964 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3459 AN: 25346

East Asian (EAS) AF: 0.244 AC: 9557 AN: 39102

South Asian (SAS) AF: 0.127 AC: 10644 AN: 83734

European-Finnish (FIN) AF: 0.170 AC: 9028 AN: 53068

Middle Eastern (MID) AF: 0.0831 AC: 380 AN: 4572

European-Non Finnish (NFE) AF: 0.208 AC: 209665 AN: 1009826

Other (OTH) AF: 0.176 AC: 9950 AN: 56384

GnomAD4 genome AF: 0.173 AC: 26347 AN: 152184 Hom.: 2475 Cov.: 33 AF XY: 0.171 AC XY: 12715 AN XY: 74394

African (AFR) AF: 0.136 AC: 5637 AN: 41528

American (AMR) AF: 0.159 AC: 2439 AN: 15292

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

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5172

South Asian (SAS) AF: 0.136 AC: 658 AN: 4822

European-Finnish (FIN) AF: 0.156 AC: 1652 AN: 10604

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

European-Non Finnish (NFE) AF: 0.203 AC: 13798 AN: 67978

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.179 Hom.: 333

Bravo AF: 0.171

Asia WGS AF: 0.163 AC: 567 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	3.4
DANN	Benign	0.54
PhyloP100		-0.67
PromoterAI		-0.0088	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs8192503; hg19: chr2-120125689; COSMIC: COSV58346962; COSMIC: COSV58346962;