Variant 19-48636925-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001352.5(DBP):c.70G>A(p.Gly24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,592,196 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 53 hom. )

Consequence

DBP
NM_001352.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.785

Variant links:

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 links:

DBP (HGNC:):

DBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073051155).

BP6

Variant 19-48636925-C-T is Benign according to our data. Variant chr19-48636925-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 712816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBP	NM_001352.5 linkuse as main transcript	c.70G>A	p.Gly24Ser	missense_variant	1/4	ENST00000222122.10	NP_001343.2	Q10586

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DBP	ENST00000222122.10 linkuse as main transcript	c.70G>A	p.Gly24Ser	missense_variant	1/4	1	NM_001352.5	ENSP00000222122.4	Q10586
DBP	ENST00000601104.1 linkuse as main transcript	c.70G>A	p.Gly24Ser	missense_variant	1/3	1		ENSP00000469291.1	M0QXP1
DBP	ENST00000594723.1 linkuse as main transcript	n.389G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

633

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00661

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00484

AC:

1023

AN:

211284

Hom.:

AF XY:

0.00491

AC XY:

566

AN XY:

115200

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00394

Gnomad ASJ exome

AF:

0.00419

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00501

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00668

Gnomad OTH exome

AF:

0.00674

GnomAD4 exome

AF:

0.00629

AC:

9063

AN:

1439886

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

4434

AN XY:

714688

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00440

Gnomad4 FIN exome

AF:

0.00344

Gnomad4 NFE exome

AF:

0.00711

Gnomad4 OTH exome

AF:

0.00579

GnomAD4 genome

AF:

0.00416

AC:

633

AN:

152310

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00428

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00783

AC:

ExAC

AF:

0.00438

AC:

525

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 01, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.79

N;.

REVEL

Benign

0.11

Sift

Benign

0.12

T;.

Sift4G

Benign

0.55

T;T

Polyphen

1.0

D;.

Vest4

0.24

MVP

0.40

MPC

1.7

ClinPred

0.028

GERP RS

3.1

Varity_R

0.050

gMVP

0.091

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over