1-3869696-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004402.4(DFFB):c.602A>G(p.Gln201Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DFFB
NM_004402.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.599

Publications

0 publications found

Variant links:

Genes affected

DFFB (HGNC:2773): (DNA fragmentation factor subunit beta) Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some of these variants has not been determined. [provided by RefSeq, Sep 2013]

DFFB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075705856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DFFB	NM_004402.4 link	c.602A>G	p.Gln201Arg	missense_variant	Exon 5 of 7	ENST00000378209.8	NP_004393.1	O76075-1Q96P73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DFFB	ENST00000378209.8 link	c.602A>G	p.Gln201Arg	missense_variant	Exon 5 of 7	1	NM_004402.4	ENSP00000367454.4		O76075-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

250326

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460900

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000134

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111698

Other (OTH)

AF:

0.0000331

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 22, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.602A>G (p.Q201R) alteration is located in exon 5 (coding exon 5) of the DFFB gene. This alteration results from a A to G substitution at nucleotide position 602, causing the glutamine (Q) at amino acid position 201 to be replaced by an arginine (R). 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

0.069

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.5

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0066

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

.;L

PhyloP100

0.60

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

.;N

REVEL

Benign

0.075

Sift

Benign

0.69

.;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;B

Vest4

0.13

MutPred

0.52

.;Gain of MoRF binding (P = 0.0521);

MVP

0.11

MPC

0.25

ClinPred

0.018

GERP RS

0.59

Varity_R

0.037

gMVP

0.34

Mutation Taster

=98/2

polymorphism

(source)

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

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1-3869696-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over