rs7226481

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013435.3(RAX):c.882A>G(p.Gln294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,579,814 control chromosomes in the GnomAD database, including 65,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5620 hom., cov: 33)

Exomes 𝑓: 0.29 ( 60218 hom. )

Consequence

RAX
NM_013435.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0410

Variant links:

Genes affected

RAX (HGNC:18662): (retina and anterior neural fold homeobox) This gene encodes a homeobox-containing transcription factor that functions in eye development. The gene is expressed early in the eye primordia, and is required for retinal cell fate determination and also regulates stem cell proliferation. Mutations in this gene have been reported in patients with defects in ocular development, including microphthalmia, anophthalmia, and coloboma.[provided by RefSeq, Oct 2009]

RAX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 18-59269163-T-C is Benign according to our data. Variant chr18-59269163-T-C is described in ClinVar as [Benign]. Clinvar id is 260310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.041 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAX	NM_013435.3 linkuse as main transcript	c.882A>G	p.Gln294=	synonymous_variant	3/3	ENST00000334889.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAX	ENST00000334889.4 linkuse as main transcript	c.882A>G	p.Gln294=	synonymous_variant	3/3	1	NM_013435.3	P1	Q9Y2V3-1
RAX	ENST00000256852.7 linkuse as main transcript	c.*313A>G		3_prime_UTR_variant	2/2	1			Q9Y2V3-2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40174

AN:

151338

Hom.:

5610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.238

AC:

44058

AN:

184906

Hom.:

5584

AF XY:

0.244

AC XY:

24858

AN XY:

101710

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.287

AC:

409521

AN:

1428360

Hom.:

60218

Cov.:

AF XY:

0.285

AC XY:

202045

AN XY:

707904

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.265

AC:

40206

AN:

151454

Hom.:

5620

Cov.:

AF XY:

0.257

AC XY:

19058

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.280

Hom.:

1967

Bravo

AF:

0.262

Asia WGS

AF:

0.238

AC:

827

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated microphthalmia 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.59

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