chr18-59267631-GCC-G

Variant names:

• chr18-59267631-GCC-G
• rs543386393
• NM_013435.3:c.*1371_*1372delGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013435.3(RAX):​c.*1371_*1372delGG 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
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
RAX	NM_013435.3	c.*1371_*1372delGG		3_prime_UTR_variant	Exon 3 of 3	ENST00000334889.4	NP_038463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAX	ENST00000334889.4	c.*1371_*1372delGG		3_prime_UTR_variant	Exon 3 of 3	1	NM_013435.3	ENSP00000334813.3
RAX	ENST00000256852.7	c.*1843_*1844delGG		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000256852.7

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

African (AFR) AF: 0.372 AC: 8453 AN: 22748

American (AMR) AF: 0.295 AC: 2227 AN: 7540

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 809 AN: 2132

East Asian (EAS) AF: 0.207 AC: 547 AN: 2640

South Asian (SAS) AF: 0.302 AC: 715 AN: 2368

European-Finnish (FIN) AF: 0.321 AC: 1188 AN: 3702

Middle Eastern (MID) AF: 0.326 AC: 43 AN: 132

European-Non Finnish (NFE) AF: 0.367 AC: 16733 AN: 45630

Other (OTH) AF: 0.360 AC: 415 AN: 1154

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs543386393; hg19: chr18-56934863; COSMIC: COSV56874368; COSMIC: COSV56874368;