Variant chr1-10461600-G-A 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_004401.3(DFFA):c.886C>T(p.Arg296Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00218 in 1,614,216 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

DFFA
NM_004401.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

DFFA (HGNC:2772): (DNA fragmentation factor subunit alpha) 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. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DFFA 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=0.014656097).

BP6

Variant 1-10461600-G-A is Benign according to our data. Variant chr1-10461600-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DFFA	NM_004401.3 linkuse as main transcript	c.886C>T	p.Arg296Cys	missense_variant	6/6	ENST00000377038.8
DFFA	NM_213566.2 linkuse as main transcript	c.*1434C>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DFFA	ENST00000377038.8 linkuse as main transcript	c.886C>T	p.Arg296Cys	missense_variant	6/6	1	NM_004401.3	P1	O00273-1
DFFA	ENST00000476658.5 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00174

AC:

437

AN:

251452

Hom.:

AF XY:

0.00166

AC XY:

226

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00228

AC:

3333

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1616

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000711

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00125

AC:

191

AN:

152326

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00149

AC:

181

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.035

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MVP

0.49

MPC

0.72

ClinPred

0.032

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.51

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