NM_001079862.4:c.*304G>C

Variant names:

• chr2-119372622-G-C
• rs2289948
• NM_001079862.4:c.*304G>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.*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
• Publications: 9 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=-0.82).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	NM_001079862.4	MANE Select	c.*304G>C		downstream_gene	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.*304G>C		downstream_gene	N/A	NP_001171488.1
	DBI	NM_001178041.4		c.*304G>C		downstream_gene	N/A	NP_001171512.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.*304G>C		downstream_gene	N/A	ENSP00000348116.3
	DBI	ENST00000627305.2	TSL:1	c.*304G>C		downstream_gene	N/A	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.*304G>C		downstream_gene	N/A	ENSP00000486281.1

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

African (AFR) AF: 0.125 AC: 489 AN: 3906

American (AMR) AF: 0.164 AC: 1060 AN: 6460

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 550 AN: 3956

East Asian (EAS) AF: 0.234 AC: 1588 AN: 6784

South Asian (SAS) AF: 0.130 AC: 3315 AN: 25592

European-Finnish (FIN) AF: 0.179 AC: 1236 AN: 6886

Middle Eastern (MID) AF: 0.0898 AC: 53 AN: 590

European-Non Finnish (NFE) AF: 0.205 AC: 18489 AN: 90006

Other (OTH) AF: 0.176 AC: 1389 AN: 7874

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

African (AFR) AF: 0.136 AC: 5654 AN: 41524

American (AMR) AF: 0.158 AC: 2416 AN: 15292

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

East Asian (EAS) AF: 0.229 AC: 1181 AN: 5162

South Asian (SAS) AF: 0.138 AC: 664 AN: 4822

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10580

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

European-Non Finnish (NFE) AF: 0.203 AC: 13803 AN: 67988

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	-0.82
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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