ENST00000824756.1:n.195G>T

Variant names:

• chr14-104766758-C-A
• rs2498804
• ENST00000824756.1:n.195G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000824756.1(ENSG00000307255):​n.195G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 455,548 control chromosomes in the GnomAD database, including 32,073 homozygotes. 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 0.34 (9104 hom., cov: 32)
  • Exomes 𝑓: 0.38 (22969 hom.)
• Consequence: ENSG00000307255 ENST00000824756.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 62 publications found

Genes affected

ENSG00000307255 (HGNC:):

SIVA1 (HGNC:17712): (SIVA1 apoptosis inducing factor) This gene encodes an E3 ubiquitin ligase that regulates cell cycle progression, cell proliferation and apoptosis. The N-terminus of this protein binds to the cytoplasmic tail of the CD27 antigen, a member of the tumor necrosis factor receptor (TNFR) superfamily. In response to UV radiation-induced DNA damage, this protein has been shown to mediate the ubiquitination of proliferating cell nuclear antigen (PCNA), an important step in translesion DNA synthesis. [provided by RefSeq, Sep 2018]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000824756.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000307255	ENST00000824756.1		n.195G>T		non_coding_transcript_exon	Exon 1 of 1
	SIVA1	ENST00000553819.5	TSL:3	n.471-32C>A		intron	N/A	ENSP00000451427.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50919 AN: 151908 Hom.: 9105 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.403 AC: 51497 AN: 127884 AF XY: 0.399

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.376 AC: 114069 AN: 303522 Hom.: 22969 Cov.: 0 AF XY: 0.381 AC XY: 65852 AN XY: 172834

African (AFR) AF: 0.268 AC: 2308 AN: 8608

American (AMR) AF: 0.505 AC: 13761 AN: 27252

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 3074 AN: 10784

East Asian (EAS) AF: 0.624 AC: 5747 AN: 9204

South Asian (SAS) AF: 0.466 AC: 27846 AN: 59700

European-Finnish (FIN) AF: 0.363 AC: 4494 AN: 12364

Middle Eastern (MID) AF: 0.371 AC: 1029 AN: 2776

European-Non Finnish (NFE) AF: 0.320 AC: 50683 AN: 158628

Other (OTH) AF: 0.361 AC: 5127 AN: 14206

GnomAD4 genome AF: 0.335 AC: 50954 AN: 152026 Hom.: 9104 Cov.: 32 AF XY: 0.343 AC XY: 25479 AN XY: 74330

African (AFR) AF: 0.268 AC: 11092 AN: 41462

American (AMR) AF: 0.439 AC: 6703 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3224 AN: 5172

South Asian (SAS) AF: 0.514 AC: 2472 AN: 4808

European-Finnish (FIN) AF: 0.354 AC: 3737 AN: 10554

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21662 AN: 67962

Other (OTH) AF: 0.335 AC: 708 AN: 2114

Alfa AF: 0.324 Hom.: 28767

Bravo AF: 0.337

Asia WGS AF: 0.562 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2498804; hg19: chr14-105233095;