ENST00000627305.2:c.117A>C

Variant names:

• chr2-119367453-A-C
• rs2084202
• ENST00000627305.2:c.117A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000627305.2(DBI):​c.117A>C​(p.Arg39Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: DBI ENST00000627305.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 14 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096993655).
• BP7: Synonymous conserved (PhyloP=-0.501 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000627305.2. 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.9+393A>C		intron	N/A	NP_001073331.1
	DBI	NM_001178017.3		c.117A>C	p.Arg39Arg	synonymous	Exon 1 of 4	NP_001171488.1
	DBI	NM_001178041.4		c.60A>C	p.Arg20Arg	synonymous	Exon 2 of 5	NP_001171512.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000627305.2	TSL:1	c.117A>C	p.Arg39Arg	synonymous	Exon 1 of 4	ENSP00000486361.1
	DBI	ENST00000627093.2	TSL:1	c.60A>C	p.Arg20Arg	synonymous	Exon 2 of 5	ENSP00000486281.1
	DBI	ENST00000460901.1	TSL:1	n.373A>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.49
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.097	T
PhyloP100		-0.50
Sift4G	Benign	0.50	T
Vest4		0.12
MVP		0.42
GERP RS		-3.8
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2084202; hg19: chr2-120125029;