14-73491111-C-A

Variant names:

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

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 id 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 FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOX1	NM_024644.5 link	c.94C>A	p.Leu32Met	missense_variant	Exon 1 of 1	ENST00000304061.8	NP_078920.2	Q9H6W3-1
HEATR4	NM_001220484.1 link	c.2844+1955G>T		intron_variant	Intron 17 of 17	ENST00000553558.6	NP_001207413.1	Q86WZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIOX1	ENST00000304061.8 link	c.94C>A	p.Leu32Met	missense_variant	Exon 1 of 1	6	NM_024644.5	ENSP00000477507.1	Q9H6W3-1
HEATR4	ENST00000553558.6 link	c.2844+1955G>T		intron_variant	Intron 17 of 17	2	NM_001220484.1	ENSP00000450444.2	Q86WZ0
HEATR4	ENST00000334988.2 link	c.2844+1955G>T		intron_variant	Intron 16 of 16	1		ENSP00000335447.2	Q86WZ0
HEATR4	ENST00000565094.1 link	n.25+645G>T		intron_variant	Intron 1 of 1	5

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

Gnomad4 AFR exome

AF:

0.0494

AC:

1627

AN:

32922

Gnomad4 AMR exome

AF:

0.00256

AC:

112

AN:

43668

Gnomad4 ASJ exome

AF:

0.0196

AC:

510

AN:

26014

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39424

Gnomad4 SAS exome

AF:

0.000118

AC:

AN:

84588

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53244

Gnomad4 NFE exome

AF:

0.000246

AC:

273

AN:

1108804

Gnomad4 Remaining exome

AF:

0.00511

AC:

307

AN:

60104

Heterozygous variant carriers

154

308

463

617

771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.0440

AC:

0.0440469

AN:

0.0440469

Gnomad4 AMR

AF:

0.00607

AC:

0.00607367

AN:

0.00607367

Gnomad4 ASJ

AF:

0.0219

AC:

0.0218894

AN:

0.0218894

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000441

AC:

0.000441047

AN:

0.000441047

Gnomad4 OTH

AF:

0.0113

AC:

0.0113422

AN:

0.0113422

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0097

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0035

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MVP

0.095

GERP RS

2.0

Varity_R

0.052

gMVP

0.14

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over