rs7226481

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013435.3(RAX):c.882A>G(p.Gln294Gln) 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:5

Conservation

PhyloP100: 0.0410

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

isolated microphthalmia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
isolated anophthalmia-microphthalmia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
coloboma
Inheritance: AR Classification: LIMITED Submitted by: G2P

RAX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
RAX	NM_013435.3 link	c.882A>G	p.Gln294Gln	synonymous_variant	Exon 3 of 3	ENST00000334889.4	NP_038463.2	Q9Y2V3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAX	ENST00000334889.4 link	c.882A>G	p.Gln294Gln	synonymous_variant	Exon 3 of 3	1	NM_013435.3	ENSP00000334813.3		Q9Y2V3-1
RAX	ENST00000256852.7 link	c.*313A>G		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000256852.7		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

GnomAD2 exomes

AF:

0.238

AC:

44058

AN:

184906

AF XY:

0.244

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 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

African (AFR)

AF:

0.262

AC:

8586

AN:

32738

American (AMR)

AF:

0.146

AC:

5824

AN:

39940

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

6924

AN:

25506

East Asian (EAS)

AF:

0.202

AC:

7731

AN:

38278

South Asian (SAS)

AF:

0.257

AC:

21435

AN:

83294

European-Finnish (FIN)

AF:

0.209

AC:

10052

AN:

48082

Middle Eastern (MID)

AF:

0.252

AC:

1321

AN:

5252

European-Non Finnish (NFE)

AF:

0.302

AC:

331525

AN:

1096234

Other (OTH)

AF:

0.273

AC:

16123

AN:

59036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

18981

37961

56942

75922

94903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11008

22016

33024

44032

55040

<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:

0.265

AC:

40206

AN:

151454

Hom.:

5620

Cov.:

AF XY:

0.257

AC XY:

19058

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.264

AC:

10908

AN:

41330

American (AMR)

AF:

0.207

AC:

3160

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

935

AN:

3456

East Asian (EAS)

AF:

0.142

AC:

728

AN:

5122

South Asian (SAS)

AF:

0.259

AC:

1245

AN:

4806

European-Finnish (FIN)

AF:

0.202

AC:

2115

AN:

10480

Middle Eastern (MID)

AF:

0.243

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.297

AC:

20127

AN:

67714

Other (OTH)

AF:

0.262

AC:

550

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1589

3179

4768

6358

7947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.280

Hom.:

1967

Bravo

AF:

0.262

Asia WGS

AF:

0.238

AC:

827

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated microphthalmia 3

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

0.041

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over