11-110091706-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645527.1(RDX):c.*757+32353T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,092 control chromosomes in the GnomAD database, including 10,525 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10525 hom., cov: 32)
• Consequence: RDX ENST00000645527.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

Genes affected

RDX (HGNC:9944): (radixin) Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RDX	ENST00000645527.1	c.*757+32353T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54988 AN: 151974 Hom.: 10520 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.362 AC: 55019 AN: 152092 Hom.: 10525 Cov.: 32 AF XY: 0.359 AC XY: 26663 AN XY: 74358

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.370

Alfa AF: 0.393 Hom.: 16690

Bravo AF: 0.358

Asia WGS AF: 0.480 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.69
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4561177; hg19: chr11-109962432;