ENST00000645527.1:n.*757+32353T>C

Variant names:

• chr11-110091706-A-G
• rs4561177
• ENST00000645527.1:n.*757+32353T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645527.1(RDX):​n.*757+32353T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 31 publications found

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]

RDX Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 24

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000306553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645527.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDX	ENST00000645527.1		n.*757+32353T>C		intron	N/A	ENSP00000496121.1	A0A2R8Y7M3
	ENSG00000306553	ENST00000819322.1		n.*6A>G		downstream_gene	N/A
	ENSG00000306553	ENST00000819323.1		n.*6A>G		downstream_gene	N/A

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

African (AFR) AF: 0.258 AC: 10721 AN: 41494

American (AMR) AF: 0.333 AC: 5084 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3468

East Asian (EAS) AF: 0.652 AC: 3374 AN: 5178

South Asian (SAS) AF: 0.361 AC: 1741 AN: 4822

European-Finnish (FIN) AF: 0.329 AC: 3484 AN: 10576

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27865 AN: 67958

Other (OTH) AF: 0.370 AC: 780 AN: 2108

Alfa AF: 0.389 Hom.: 22063

Bravo AF: 0.358

Asia WGS AF: 0.480 AC: 1670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.69
DANN	Benign	0.70
PhyloP100		0.024

Splicing

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

Other links and lift over

dbSNP: rs4561177; hg19: chr11-109962432;