Variant 7-87907714-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006716.4(DBF4):c.1576A>G(p.Ile526Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,614,072 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 20 hom. )

Consequence

DBF4
NM_006716.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.88

Variant links:

Genes affected

DBF4 (HGNC:17364): (DBF4-CDC7 kinase regulatory subunit) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

DBF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021000504).

BP6

Variant 7-87907714-A-G is Benign according to our data. Variant chr7-87907714-A-G is described in ClinVar as [Benign]. Clinvar id is 790355.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DBF4	NM_006716.4 linkuse as main transcript	c.1576A>G	p.Ile526Val	missense_variant	12/12	ENST00000265728.6
DBF4	NM_001318061.2 linkuse as main transcript	c.904A>G	p.Ile302Val	missense_variant	12/12
DBF4	NM_001318060.2 linkuse as main transcript	c.877A>G	p.Ile293Val	missense_variant	11/11
DBF4	NM_001318062.2 linkuse as main transcript	c.796A>G	p.Ile266Val	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBF4	ENST00000265728.6 linkuse as main transcript	c.1576A>G	p.Ile526Val	missense_variant	12/12	1	NM_006716.4	P1	Q9UBU7-1
DBF4	ENST00000413643.5 linkuse as main transcript	c.*810A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	1			Q9UBU7-2
DBF4	ENST00000431138.5 linkuse as main transcript	c.*1349A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	1

Frequencies

GnomAD3 genomes

AF:

0.00367

AC:

558

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00459

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00473

AC:

1188

AN:

250966

Hom.:

AF XY:

0.00480

AC XY:

652

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000865

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.00648

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00404

AC:

5899

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2823

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.00366

AC:

558

AN:

152286

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00204

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00560

AC:

680

EpiCase

AF:

0.00262

EpiControl

AF:

0.00290

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.68

DEOGEN2

Benign

0.019

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

0.21

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.012

MVP

0.18

MPC

0.12

ClinPred

0.011

GERP RS

-10

Varity_R

0.020

gMVP

0.049

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