rs8192504

Variant names:

• chr2-119368293-G-A
• rs8192504
• NM_001079862.4:c.115G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-119368293-G-A
• chr2-119368293-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001079862.4(DBI):​c.115G>A​(p.Asp39Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00307 in 1,613,014 control chromosomes in the GnomAD database, including 47 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 0.0039 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (37 hom.)
• Consequence: DBI NM_001079862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• Publications: 10 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007935107).
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.115G>A	p.Asp39Asn	missense	Exon 2 of 4	NP_001073331.1	P07108-1
	DBI	NM_001178017.3		c.298G>A	p.Asp100Asn	missense	Exon 2 of 4	NP_001171488.1	P07108-5
	DBI	NM_001178041.4		c.241G>A	p.Asp81Asn	missense	Exon 3 of 5	NP_001171512.1	P07108-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBI	ENST00000355857.8	TSL:1 MANE Select	c.115G>A	p.Asp39Asn	missense	Exon 2 of 4	ENSP00000348116.3	P07108-1
	DBI	ENST00000627305.2	TSL:1	c.298G>A	p.Asp100Asn	missense	Exon 2 of 4	ENSP00000486361.1	P07108-5
	DBI	ENST00000627093.2	TSL:1	c.241G>A	p.Asp81Asn	missense	Exon 3 of 5	ENSP00000486281.1	P07108-4

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 600 AN: 152168 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00454 AC: 1141 AN: 251458 AF XY: 0.00452

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00298 AC: 4354 AN: 1460728 Hom.: 37 Cov.: 32 AF XY: 0.00292 AC XY: 2124 AN XY: 726752

African (AFR) AF: 0.000299 AC: 10 AN: 33444

American (AMR) AF: 0.000581 AC: 26 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000615 AC: 53 AN: 86224

European-Finnish (FIN) AF: 0.0303 AC: 1616 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5762

European-Non Finnish (NFE) AF: 0.00224 AC: 2494 AN: 1110992

Other (OTH) AF: 0.00234 AC: 141 AN: 60348

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152286 Hom.: 10 Cov.: 33 AF XY: 0.00516 AC XY: 384 AN XY: 74444

African (AFR) AF: 0.000337 AC: 14 AN: 41574

American (AMR) AF: 0.000719 AC: 11 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00304 AC: 207 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00244 Hom.: 1

Bravo AF: 0.00155

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00398 AC: 483

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.84	T
PhyloP100		7.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.20
Sift	Benign	0.075	T
Sift4G	Uncertain	0.045	D
Polyphen		0.89	P
Vest4		0.69
MVP		0.64
MPC		1.1
ClinPred		0.046	T
GERP RS		4.6
Varity_R		0.67
gMVP		0.50
Mutation Taster		=80/20	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: rs8192504; hg19: chr2-120125869; COSMIC: COSV58346617; COSMIC: COSV58346617;