rs1057026

Variant names:

• chr1-10461197-T-C
• rs1057026
• NM_004401.3:c.*293A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004401.3(DFFA):​c.*293A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 322,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: DFFA NM_004401.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004401.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DFFA	NM_004401.3	MANE Select	c.*293A>G		3_prime_UTR	Exon 6 of 6	NP_004392.1	O00273-1
	DFFA	NM_213566.2		c.*1837A>G		3_prime_UTR	Exon 5 of 5	NP_998731.1	O00273-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DFFA	ENST00000377038.8	TSL:1 MANE Select	c.*293A>G		3_prime_UTR	Exon 6 of 6	ENSP00000366237.3	O00273-1
	DFFA	ENST00000866602.1		c.*293A>G		3_prime_UTR	Exon 6 of 6	ENSP00000536661.1
	DFFA	ENST00000866603.1		c.*293A>G		3_prime_UTR	Exon 5 of 5	ENSP00000536662.1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000588 AC: 100 AN: 169996 Hom.: 0 Cov.: 4 AF XY: 0.000654 AC XY: 58 AN XY: 88658

African (AFR) AF: 0.000300 AC: 2 AN: 6656

American (AMR) AF: 0.000238 AC: 2 AN: 8396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5240

East Asian (EAS) AF: 0.00250 AC: 28 AN: 11216

South Asian (SAS) AF: 0.000407 AC: 7 AN: 17214

European-Finnish (FIN) AF: 0.000517 AC: 4 AN: 7732

Middle Eastern (MID) AF: 0.00161 AC: 1 AN: 620

European-Non Finnish (NFE) AF: 0.000494 AC: 51 AN: 103332

Other (OTH) AF: 0.000521 AC: 5 AN: 9590

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74450

African (AFR) AF: 0.000385 AC: 16 AN: 41566

American (AMR) AF: 0.000458 AC: 7 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000741 Hom.: 0

Bravo AF: 0.000665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.43
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1057026; hg19: chr1-10521254;