18-59267631-GCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013435.3(RAX):c.*1371_*1372del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (4717 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: RAX NM_013435.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510

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 -10 ACMG points.

• BP6: Variant 18-59267631-GCC-G is Benign according to our data. Variant chr18-59267631-GCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 327514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAX	NM_013435.3	c.*1371_*1372del		3_prime_UTR_variant	3/3	ENST00000334889.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAX	ENST00000334889.4	c.*1371_*1372del		3_prime_UTR_variant	3/3	1	NM_013435.3	P1
RAX	ENST00000256852.7	c.*1843_*1844del		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 31399 AN: 88692 Hom.: 4715 Cov.: 0

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 31407 AN: 88706 Hom.: 4717 Cov.: 0 AF XY: 0.348 AC XY: 14199 AN XY: 40828

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.360

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs543386393; hg19: chr18-56934863;