rs2498804

Positions:

• chr14-104766758-C-A
• chr14-104766758-C-G
• chr14-104766758-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007064362.1(LOC102723342):​n.1944C>A 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: LOC102723342 XR_007064362.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

Genes affected

LOC102723342 (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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC102723342	XR_007064362.1	n.1944C>A		non_coding_transcript_exon_variant	1/2
LOC107987209	XR_001750915.3	n.107+85G>T		intron_variant, non_coding_transcript_variant
LOC102723342	XR_429419.5	n.1944C>A		non_coding_transcript_exon_variant	1/3
LOC107987209	XR_001750914.3	n.107+85G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIVA1	ENST00000553819.5	c.471-32C>A		intron_variant, NMD_transcript_variant		3

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

GnomAD3 exomes AF: 0.403 AC: 51497 AN: 127884 Hom.: 11312 AF XY: 0.399 AC XY: 27932 AN XY: 70036

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 SAS exome AF: 0.469

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

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.361

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.335

Alfa AF: 0.319 Hom.: 11934

Bravo AF: 0.337

Asia WGS AF: 0.562 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2498804; hg19: chr14-105233095;