Variant 7-87907292-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006716.4(DBF4):c.1154G>T(p.Cys385Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DBF4
NM_006716.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.279

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028317392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBF4	NM_006716.4 linkuse as main transcript	c.1154G>T	p.Cys385Phe	missense_variant	12/12	ENST00000265728.6	NP_006707.1	Q9UBU7-1
DBF4	NM_001318061.2 linkuse as main transcript	c.482G>T	p.Cys161Phe	missense_variant	12/12		NP_001304990.1	Q9UBU7B7Z8C6
DBF4	NM_001318060.2 linkuse as main transcript	c.455G>T	p.Cys152Phe	missense_variant	11/11		NP_001304989.1	Q9UBU7B4DXK0
DBF4	NM_001318062.2 linkuse as main transcript	c.374G>T	p.Cys125Phe	missense_variant	12/12		NP_001304991.1	Q9UBU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6 linkuse as main transcript	c.1154G>T	p.Cys385Phe	missense_variant	12/12	1	NM_006716.4	ENSP00000265728.1		Q9UBU7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251040

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727134

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.41

DANN

Benign

0.29

DEOGEN2

Benign

0.019

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.32

M_CAP

Benign

0.0030

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.7

PrimateAI

Benign

0.23

PROVEAN

Benign

0.10

REVEL

Benign

0.0060

Sift

Benign

0.71

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.045

MutPred

0.15

Gain of helix (P = 0.0496);

MVP

0.082

MPC

0.23

ClinPred

0.027

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.071

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