rs12608544

chr19-48633394-G-A

Variant summary

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

The ENST00000601104.1(DBP):c.*23C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,576,216 control chromosomes in the GnomAD database, including 6,137 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 0.11 (1374 hom., cov: 32)
  • Exomes 𝑓: 0.058 (4763 hom.)
• Consequence: DBP ENST00000601104.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

DBP (HGNC:2697): (D-box binding PAR bZIP transcription factor) The protein encoded by this gene is a member of the PAR bZIP transcription factor family and binds to specific sequences in the promoters of several genes, such as albumin, CYP2A4, and CYP2A5. The encoded protein can bind DNA as a homo- or heterodimer and is involved in the regulation of some circadian rhythm genes. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBP	NM_001352.5	c.762+50C>T		intron_variant		ENST00000222122.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBP	ENST00000222122.10	c.762+50C>T		intron_variant		1	NM_001352.5	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16132 AN: 152054 Hom.: 1367 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0984 AC: 24639 AN: 250446 Hom.: 2102 AF XY: 0.0944 AC XY: 12786 AN XY: 135474

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.294

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0464

Gnomad NFE exome AF: 0.0381

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0579 AC: 82384 AN: 1424042 Hom.: 4763 Cov.: 26 AF XY: 0.0594 AC XY: 42248 AN XY: 710748

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0720

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.106 AC: 16172 AN: 152174 Hom.: 1374 Cov.: 32 AF XY: 0.108 AC XY: 8051 AN XY: 74396

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0714

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0471

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0574 Hom.: 399

Bravo AF: 0.116

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.79
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs12608544; hg19: chr19-49136651; COSMIC: COSV50033147; COSMIC: COSV50033147;