5-97176979-A-G

Variant names:

• chr5-97176979-A-G
• rs2544771
• NM_018343.3:c.498+137T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018343.3. 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
	RIOK2	NM_018343.3	MANE Select	c.498+137T>C		intron	N/A	NP_060813.2
	RIOK2	NM_001159749.2		c.498+137T>C		intron	N/A	NP_001153221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOK2	ENST00000283109.8	TSL:1 MANE Select	c.498+137T>C		intron	N/A	ENSP00000283109.3
	RIOK2	ENST00000508447.1	TSL:1	c.498+137T>C		intron	N/A	ENSP00000420932.1
	RIOK2	ENST00000924329.1		c.498+137T>C		intron	N/A	ENSP00000594388.1

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

African (AFR) AF: 0.673 AC: 9378 AN: 13926

American (AMR) AF: 0.600 AC: 12970 AN: 21624

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 11050 AN: 16716

East Asian (EAS) AF: 0.636 AC: 20823 AN: 32728

South Asian (SAS) AF: 0.696 AC: 36782 AN: 52820

European-Finnish (FIN) AF: 0.753 AC: 25236 AN: 33506

Middle Eastern (MID) AF: 0.597 AC: 1303 AN: 2184

European-Non Finnish (NFE) AF: 0.669 AC: 239020 AN: 357368

Other (OTH) AF: 0.671 AC: 19835 AN: 29578

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

African (AFR) AF: 0.680 AC: 28176 AN: 41458

American (AMR) AF: 0.639 AC: 9759 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2283 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3362 AN: 5162

South Asian (SAS) AF: 0.694 AC: 3346 AN: 4818

European-Finnish (FIN) AF: 0.756 AC: 8002 AN: 10584

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46211 AN: 67962

Other (OTH) AF: 0.639 AC: 1350 AN: 2114

Alfa AF: 0.674 Hom.: 149817

Bravo AF: 0.666

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.38
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2544771; hg19: chr5-96512683;