14-104755700-C-T

Variant names:

• chr14-104755700-C-T
• rs1132975
• NM_006427.4:c.189C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006427.4(SIVA1):​c.189C>T​(p.Ala63Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,528 control chromosomes in the GnomAD database, including 102,285 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 0.35 (9569 hom., cov: 33)
  • Exomes 𝑓: 0.35 (92716 hom.)
• Consequence: SIVA1 NM_006427.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 45 publications found

Genes affected

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]

LOC107987209 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.007).
• BP7: Synonymous conserved (PhyloP=-0.253 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006427.4. 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
	SIVA1	NM_006427.4	MANE Select	c.189C>T	p.Ala63Ala	synonymous	Exon 2 of 4	NP_006418.2
	SIVA1	NM_021709.3		c.119-904C>T		intron	N/A	NP_068355.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIVA1	ENST00000329967.11	TSL:1 MANE Select	c.189C>T	p.Ala63Ala	synonymous	Exon 2 of 4	ENSP00000329213.6
	SIVA1	ENST00000347067.9	TSL:1	c.119-904C>T		intron	N/A	ENSP00000329447.6
	SIVA1	ENST00000554013.1	TSL:1	n.140-904C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52452 AN: 151968 Hom.: 9571 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.394 AC: 99069 AN: 251212 AF XY: 0.391

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.349 AC: 510120 AN: 1461440 Hom.: 92716 Cov.: 39 AF XY: 0.352 AC XY: 255677 AN XY: 727046

African (AFR) AF: 0.268 AC: 8980 AN: 33468

American (AMR) AF: 0.510 AC: 22782 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7876 AN: 26128

East Asian (EAS) AF: 0.576 AC: 22869 AN: 39694

South Asian (SAS) AF: 0.462 AC: 39807 AN: 86244

European-Finnish (FIN) AF: 0.372 AC: 19851 AN: 53396

Middle Eastern (MID) AF: 0.374 AC: 2128 AN: 5694

European-Non Finnish (NFE) AF: 0.327 AC: 364060 AN: 1111760

Other (OTH) AF: 0.361 AC: 21767 AN: 60378

GnomAD4 genome AF: 0.345 AC: 52484 AN: 152088 Hom.: 9569 Cov.: 33 AF XY: 0.352 AC XY: 26166 AN XY: 74338

African (AFR) AF: 0.271 AC: 11267 AN: 41510

American (AMR) AF: 0.447 AC: 6837 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3148 AN: 5150

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4814

European-Finnish (FIN) AF: 0.367 AC: 3880 AN: 10586

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22736 AN: 67948

Other (OTH) AF: 0.349 AC: 737 AN: 2112

Alfa AF: 0.338 Hom.: 26829

Bravo AF: 0.346

Asia WGS AF: 0.536 AC: 1863 AN: 3478

EpiCase AF: 0.348

EpiControl AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1132975; hg19: chr14-105222037; COSMIC: COSV57331678;