5-97176979-A-G

Position:

• chr5-97176979-A-G

Variant summary

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

The NM_018343.3(RIOK2):​c.498+137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 712,506 control chromosomes in the GnomAD database, including 162,216 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 0.68 (35241 hom., cov: 32)
  • Exomes 𝑓: 0.67 (126975 hom.)
• Consequence: RIOK2 NM_018343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

RIOK2 (HGNC:18999): (RIO kinase 2) Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIOK2	NM_018343.3	c.498+137T>C		intron_variant		ENST00000283109.8
RIOK2	NM_001159749.2	c.498+137T>C		intron_variant
RIOK2	XM_017009628.2	c.-163+137T>C		intron_variant
LIX1-AS1	XR_007058883.1	n.4605-6029A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIOK2	ENST00000283109.8	c.498+137T>C		intron_variant		1	NM_018343.3	P1
RIOK2	ENST00000508447.1	c.498+137T>C		intron_variant		1
LIX1-AS1	ENST00000504578.2	n.574-6029A>G		intron_variant, non_coding_transcript_variant		5
RIOK2	ENST00000508991.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103212 AN: 151938 Hom.: 35190 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.672 AC: 376397 AN: 560450 Hom.: 126975 Cov.: 7 AF XY: 0.674 AC XY: 202937 AN XY: 301074

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.753

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.680 AC: 103328 AN: 152056 Hom.: 35241 Cov.: 32 AF XY: 0.683 AC XY: 50765 AN XY: 74322

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.639

Alfa AF: 0.673 Hom.: 71647

Bravo AF: 0.666

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs2544771; hg19: chr5-96512683;