Variant rs777929939 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_013435.3(RAX):c.729C>A(p.Ser243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,298,344 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

RAX
NM_013435.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.410

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 18-59269316-G-T is Benign according to our data. Variant chr18-59269316-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 468922.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00124 (187/150914) while in subpopulation AFR AF= 0.0044 (182/41392). AF 95% confidence interval is 0.00387. There are 2 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAX	NM_013435.3 linkuse as main transcript	c.729C>A	p.Ser243=	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.729C>A	p.Ser243=	synonymous_variant	3/3	1	NM_013435.3	P1	Q9Y2V3-1
RAX	ENST00000256852.7 linkuse as main transcript	c.*160C>A		3_prime_UTR_variant	2/2	1			Q9Y2V3-2

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

190

AN:

150806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000184

AC:

AN:

10890

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

6528

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.000498

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

124

AN:

1147430

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

556036

show subpopulations

Gnomad4 AFR exome

AF:

0.00462

Gnomad4 AMR exome

AF:

0.000197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000104

Gnomad4 OTH exome

AF:

0.000305

GnomAD4 genome

AF:

0.00124

AC:

187

AN:

150914

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

73722

show subpopulations

Gnomad4 AFR

AF:

0.00440

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.00116

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Isolated microphthalmia 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.4

DANN

Benign

0.92

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