19-48636952-G-C

Position:

• chr19-48636952-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001352.5(DBP):​c.43C>G​(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,403,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: DBP NM_001352.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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]

DBP (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23154837).
• BS2: High AC in GnomAdExome4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBP	NM_001352.5	c.43C>G	p.Leu15Val	missense_variant	1/4	ENST00000222122.10	NP_001343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBP	ENST00000222122.10	c.43C>G	p.Leu15Val	missense_variant	1/4	1	NM_001352.5	ENSP00000222122.4
DBP	ENST00000601104.1	c.43C>G	p.Leu15Val	missense_variant	1/3	1		ENSP00000469291.1
DBP	ENST00000594723.1	n.362C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000428 AC: 60 AN: 1403244 Hom.: 0 Cov.: 31 AF XY: 0.0000461 AC XY: 32 AN XY: 693584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000544

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.43C>G (p.L15V) alteration is located in exon 1 (coding exon 1) of the DBP gene. This alteration results from a C to G substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.47	N;.
REVEL	Benign	0.045
Sift	Uncertain	0.011	D;.
Sift4G	Benign	0.28	T;T
Polyphen		0.89	P;.
Vest4		0.38
MutPred		0.27		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.33
MPC		1.2
ClinPred		0.79	D
GERP RS		3.6
Varity_R		0.24
gMVP		0.091

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2030832225; hg19: chr19-49140209;