rs73362602

Positions:

• chr14-104764258-T-C
• chr14-104764258-T-G

Variant summary

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

The XR_001750915.3(LOC107987209):​n.107+2585A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,866 control chromosomes in the GnomAD database, including 32,626 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 0.63 (32626 hom., cov: 32)
• Consequence: LOC107987209 XR_001750915.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

Genes affected

LOC107987209 (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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107987209	XR_001750915.3	n.107+2585A>G		intron_variant, non_coding_transcript_variant
LOC107987209	XR_001750914.3	n.107+2585A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIVA1	ENST00000553819.5	c.471-2532T>C		intron_variant, NMD_transcript_variant		3		ENSP00000451427

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95770 AN: 151748 Hom.: 32581 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.600

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 95871 AN: 151866 Hom.: 32626 Cov.: 32 AF XY: 0.633 AC XY: 46944 AN XY: 74198

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.599

Alfa AF: 0.576 Hom.: 3346

Bravo AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73362602; hg19: chr14-105230595;