dbSNP rs73293424: RIOX1:p.Leu32Met (chr14-73491111-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024644.5(RIOX1):c.94C>A(p.Leu32Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,606,864 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 65 hom. )

Consequence

RIOX1
NM_024644.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.687

Publications

3 publications found

Variant links:

Genes affected

RIOX1 (HGNC:20968): (ribosomal oxygenase 1) Predicted to enable histone H3-methyl-lysine-36 demethylase activity; histone H3-methyl-lysine-4 demethylase activity; and iron ion binding activity. Predicted to be involved in histone lysine demethylation; negative regulation of osteoblast differentiation; and negative regulation of transcription, DNA-templated. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

RIOX1 links:

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACOT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034736693).

BP6

Variant 14-73491111-C-A is Benign according to our data. Variant chr14-73491111-C-A is described in ClinVar as Benign. ClinVar VariationId is 768664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2055/152348) while in subpopulation AFR AF = 0.044 (1832/41592). AF 95% confidence interval is 0.0424. There are 45 homozygotes in GnomAd4. There are 988 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024644.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIOX1	NM_024644.5	MANE Select	c.94C>A	p.Leu32Met	missense	Exon 1 of 1	NP_078920.2	Q9H6W3-1
HEATR4	NM_001220484.1	MANE Select	c.2844+1955G>T		intron	N/A	NP_001207413.1	Q86WZ0
HEATR4	NM_203309.2		c.2844+1955G>T		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIOX1	ENST00000304061.8	TSL:6 MANE Select	c.94C>A	p.Leu32Met	missense	Exon 1 of 1	ENSP00000477507.1	Q9H6W3-1
HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.2844+1955G>T		intron	N/A	ENSP00000450444.2	Q86WZ0
HEATR4	ENST00000334988.2	TSL:1	c.2844+1955G>T		intron	N/A	ENSP00000335447.2	Q86WZ0

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2049

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0440

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00400

AC:

958

AN:

239778

AF XY:

0.00328

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000477

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.00197

AC:

2865

AN:

1454516

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1283

AN XY:

723376

show subpopulations

African (AFR)

AF:

0.0494

AC:

1627

AN:

32922

American (AMR)

AF:

0.00256

AC:

112

AN:

43668

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

510

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39424

South Asian (SAS)

AF:

0.000118

AC:

AN:

84588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00452

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000246

AC:

273

AN:

1108804

Other (OTH)

AF:

0.00511

AC:

307

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

154

308

463

617

771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0135

AC:

2055

AN:

152348

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

988

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0440

AC:

1832

AN:

41592

American (AMR)

AF:

0.00607

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68020

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.0155

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0353

AC:

136

ESP6500EA

AF:

0.000727

AC:

ExAC

AF:

0.00421

AC:

509

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0097

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0035

PhyloP100

0.69

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MVP

0.095

GERP RS

2.0

PromoterAI

-0.15

Neutral

(source)

Varity_R

0.052

gMVP

0.14

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over