18-59267126-A-G

Position:

• chr18-59267126-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013435.3(RAX):​c.*1878T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,176 control chromosomes in the GnomAD database, including 5,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5003 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: RAX NM_013435.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.137

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-59267126-A-G is Benign according to our data. Variant chr18-59267126-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 327501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAX	NM_013435.3	c.*1878T>C		3_prime_UTR_variant	3/3	ENST00000334889.4	NP_038463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAX	ENST00000334889.4	c.*1878T>C		3_prime_UTR_variant	3/3	1	NM_013435.3	ENSP00000334813	P1
RAX	ENST00000256852.7	c.*2350T>C		3_prime_UTR_variant	2/2	1		ENSP00000256852

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37695 AN: 152052 Hom.: 4994 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.248 AC: 37721 AN: 152170 Hom.: 5003 Cov.: 33 AF XY: 0.241 AC XY: 17950 AN XY: 74408

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.256

Alfa AF: 0.284 Hom.: 10923

Bravo AF: 0.242

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Isolated microphthalmia 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs9947104; hg19: chr18-56934358;