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GeneBe

1-10461586-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004401.3(DFFA):c.900G>A(p.Thr300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,614,232 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

DFFA
NM_004401.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.99
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-10461586-C-T is Benign according to our data. Variant chr1-10461586-C-T is described in ClinVar as [Benign]. Clinvar id is 782903.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.99 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DFFANM_004401.3 linkuse as main transcriptc.900G>A p.Thr300= synonymous_variant 6/6 ENST00000377038.8
DFFANM_213566.2 linkuse as main transcriptc.*1448G>A 3_prime_UTR_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DFFAENST00000377038.8 linkuse as main transcriptc.900G>A p.Thr300= synonymous_variant 6/61 NM_004401.3 P1O00273-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00378
AC:
576
AN:
152228
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0130
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00123
AC:
309
AN:
251448
Hom.:
2
AF XY:
0.00105
AC XY:
143
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0118
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00268
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.000832
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000560
AC:
819
AN:
1461886
Hom.:
3
Cov.:
31
AF XY:
0.000518
AC XY:
377
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0119
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.00214
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.000543
Gnomad4 NFE exome
AF:
0.000153
Gnomad4 OTH exome
AF:
0.00132
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00377
AC:
575
AN:
152346
Hom.:
8
Cov.:
32
AF XY:
0.00365
AC XY:
272
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0129
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000403
Hom.:
0
Bravo
AF:
0.00418
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

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 submitterclinical testingInvitaeSep 29, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
1.5
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs78256349; hg19: chr1-10521643; API