rs2271733

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013435.3(RAX):c.132C>A(p.Asp44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,534,892 control chromosomes in the GnomAD database, including 61,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4596 hom., cov: 33)

Exomes 𝑓: 0.28 ( 56574 hom. )

Consequence

RAX
NM_013435.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.892

Publications

21 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)
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

new If you want to explore the variant's impact on the transcript NM_013435.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0028769076).

BP6

Variant 18-59273075-G-T is Benign according to our data. Variant chr18-59273075-G-T is described in ClinVar as Benign. ClinVar VariationId is 260309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013435.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAX	NM_013435.3	MANE Select	c.132C>A	p.Asp44Glu	missense	Exon 1 of 3	NP_038463.2	Q9Y2V3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAX	ENST00000334889.4	TSL:1 MANE Select	c.132C>A	p.Asp44Glu	missense	Exon 1 of 3	ENSP00000334813.3	Q9Y2V3-1
RAX	ENST00000256852.7	TSL:1	c.132C>A	p.Asp44Glu	missense	Exon 1 of 2	ENSP00000256852.7	Q9Y2V3-2
RAX	ENST00000555288.1	TSL:3	c.132C>A	p.Asp44Glu	missense	Exon 2 of 2	ENSP00000450583.1	G3V2C8

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35733

AN:

152054

Hom.:

4594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.224

AC:

29462

AN:

131492

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.282

AC:

389830

AN:

1382726

Hom.:

56574

Cov.:

AF XY:

0.280

AC XY:

191322

AN XY:

682316

show subpopulations

African (AFR)

AF:

0.161

AC:

5086

AN:

31530

American (AMR)

AF:

0.144

AC:

5130

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

6844

AN:

25140

East Asian (EAS)

AF:

0.206

AC:

7358

AN:

35692

South Asian (SAS)

AF:

0.231

AC:

18310

AN:

79190

European-Finnish (FIN)

AF:

0.211

AC:

7078

AN:

33606

Middle Eastern (MID)

AF:

0.244

AC:

1389

AN:

5684

European-Non Finnish (NFE)

AF:

0.300

AC:

323402

AN:

1078354

Other (OTH)

AF:

0.263

AC:

15233

AN:

57846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

19198

38397

57595

76794

95992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10812

21624

32436

43248

54060

<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:

0.235

AC:

35732

AN:

152166

Hom.:

4596

Cov.:

AF XY:

0.228

AC XY:

16964

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.168

AC:

6968

AN:

41572

American (AMR)

AF:

0.195

AC:

2989

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

934

AN:

3466

East Asian (EAS)

AF:

0.140

AC:

716

AN:

5128

South Asian (SAS)

AF:

0.232

AC:

1118

AN:

4828

European-Finnish (FIN)

AF:

0.200

AC:

2122

AN:

10596

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.293

AC:

19937

AN:

67972

Other (OTH)

AF:

0.244

AC:

514

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1445

2890

4336

5781

7226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.277

Hom.:

12603

Bravo

AF:

0.228

Asia WGS

AF:

0.226

AC:

786

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Isolated microphthalmia 3 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.041

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-0.89

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Benign

0.64

Sift4G

Benign

0.68

PromoterAI

0.0044

Neutral

(source)

Varity_R

0.035

gMVP

0.34

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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