Variant 14-73492604-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024644.5(RIOX1):c.1587C>G(p.Arg529=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,872 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 7 hom. )

Consequence

RIOX1
NM_024644.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.249

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:):

ACOT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 14-73492604-C-G is Benign according to our data. Variant chr14-73492604-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 788892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.249 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOX1	NM_024644.5 linkuse as main transcript	c.1587C>G	p.Arg529=	synonymous_variant	1/1	ENST00000304061.8	NP_078920.2
HEATR4	NM_001220484.1 linkuse as main transcript	c.2844+462G>C		intron_variant		ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOX1	ENST00000304061.8 linkuse as main transcript	c.1587C>G	p.Arg529=	synonymous_variant	1/1		NM_024644.5	ENSP00000477507	P1	Q9H6W3-1
HEATR4	ENST00000553558.6 linkuse as main transcript	c.2844+462G>C		intron_variant		2	NM_001220484.1	ENSP00000450444	P1
HEATR4	ENST00000334988.2 linkuse as main transcript	c.2844+462G>C		intron_variant		1		ENSP00000335447	P1

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

372

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00237

AC:

591

AN:

249166

Hom.:

AF XY:

0.00240

AC XY:

325

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00283

AC:

4140

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

2036

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00223

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152178

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00308

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 23, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	RIOX1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.3

DANN

Benign

0.75

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