rs8192501

Variant names:

• chr2-119367739-G-A
• rs8192501
• ENST00000393103.2:c.-181G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-119367739-G-A
• chr2-119367739-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000393103.2(DBI):​c.-181G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,607,268 control chromosomes in the GnomAD database, including 793 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 0.021 (48 hom., cov: 32)
  • Exomes 𝑓: 0.028 (745 hom.)
• Consequence: DBI ENST00000393103.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 8 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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0209 (3177/152258) while in subpopulation NFE AF = 0.0325 (2207/68006). AF 95% confidence interval is 0.0313. There are 48 homozygotes in GnomAd4. There are 1444 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393103.2. 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.10-449G>A		intron	N/A	NP_001073331.1
	DBI	NM_001079863.3		c.-181G>A		5_prime_UTR	Exon 1 of 4	NP_001073332.1
	DBI	NM_001178017.3		c.192+211G>A		intron	N/A	NP_001171488.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000393103.2	TSL:1	c.-181G>A		5_prime_UTR	Exon 1 of 4	ENSP00000376815.2
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.10-449G>A		intron	N/A	ENSP00000348116.3
	DBI	ENST00000627305.2	TSL:1	c.192+211G>A		intron	N/A	ENSP00000486361.1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3177 AN: 152140 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0281 AC: 40948 AN: 1455010 Hom.: 745 Cov.: 50 AF XY: 0.0278 AC XY: 20069 AN XY: 723060

African (AFR) AF: 0.00381 AC: 127 AN: 33314

American (AMR) AF: 0.0160 AC: 706 AN: 44092

Ashkenazi Jewish (ASJ) AF: 0.0500 AC: 1289 AN: 25786

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39560

South Asian (SAS) AF: 0.00997 AC: 856 AN: 85898

European-Finnish (FIN) AF: 0.0118 AC: 624 AN: 53104

Middle Eastern (MID) AF: 0.0163 AC: 87 AN: 5330

European-Non Finnish (NFE) AF: 0.0321 AC: 35529 AN: 1107894

Other (OTH) AF: 0.0288 AC: 1729 AN: 60032

GnomAD4 genome AF: 0.0209 AC: 3177 AN: 152258 Hom.: 48 Cov.: 32 AF XY: 0.0194 AC XY: 1444 AN XY: 74444

African (AFR) AF: 0.00520 AC: 216 AN: 41570

American (AMR) AF: 0.0233 AC: 357 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4820

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0325 AC: 2207 AN: 68006

Other (OTH) AF: 0.0294 AC: 62 AN: 2110

Alfa AF: 0.00706 Hom.: 3

Bravo AF: 0.0212

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		-0.33
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism

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: rs8192501; hg19: chr2-120125315; COSMIC: COSV58347655; COSMIC: COSV58347655;