rs2289948

Variant names:

• chr2-119372622-G-C
• rs2289948
• NM_001079862.4:c.*304G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-119372622-G-C
• chr2-119372622-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079862.4(DBI):​c.*304G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 304,212 control chromosomes in the GnomAD database, including 5,226 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 (2465 hom., cov: 33)
  • Exomes 𝑓: 0.19 (2761 hom.)
• Consequence: DBI NM_001079862.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBI	NM_001079862.4	c.*304G>C		downstream_gene_variant		ENST00000355857.8	NP_001073331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBI	ENST00000355857.8	c.*304G>C		downstream_gene_variant		1	NM_001079862.4	ENSP00000348116.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26330 AN: 152040 Hom.: 2464 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.185 AC: 28169 AN: 152054 Hom.: 2761 AF XY: 0.178 AC XY: 14703 AN XY: 82574

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.173 AC: 26345 AN: 152158 Hom.: 2465 Cov.: 33 AF XY: 0.171 AC XY: 12716 AN XY: 74384

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.154

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2289948; hg19: chr2-120130198; COSMIC: COSV61055253;