dbSNP rs8192501: DBI:c.-181G>A (chr2-119367739-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001079863.3(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
NM_001079863.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

Variant links:

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]

DBI links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBI	NM_001079862.4 link	c.10-449G>A		intron_variant	Intron 1 of 3	ENST00000355857.8	NP_001073331.1	P07108-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBI	ENST00000355857.8 link	c.10-449G>A		intron_variant	Intron 1 of 3	1	NM_001079862.4	ENSP00000348116.3		P07108-1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3177

AN:

152140

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0278

AC XY:

20069

AN XY:

723060

show subpopulations

Gnomad4 AFR exome

AF:

0.00381

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.0500

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00997

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0288

GnomAD4 genome

AF:

0.0209

AC:

3177

AN:

152258

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1444

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00520

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0548

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00895

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.00706

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

DANN

Benign

0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over