rs1676536

Variant names:

• chr11-110291705-T-C
• rs1676536
• NM_002906.4:c.-65+4762A>G

Variant summary

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

The NM_002906.4(RDX):​c.-65+4762A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,036 control chromosomes in the GnomAD database, including 5,700 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 0.24 (5700 hom., cov: 31)
• Consequence: RDX NM_002906.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 3 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDX	NM_002906.4	c.-65+4762A>G		intron_variant	Intron 1 of 13	ENST00000645495.2	NP_002897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDX	ENST00000645495.2	c.-65+4762A>G		intron_variant	Intron 1 of 13		NM_002906.4	ENSP00000496503.2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36435 AN: 151918 Hom.: 5699 Cov.: 31

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.240 AC: 36430 AN: 152036 Hom.: 5700 Cov.: 31 AF XY: 0.237 AC XY: 17617 AN XY: 74296

African (AFR) AF: 0.0626 AC: 2597 AN: 41494

American (AMR) AF: 0.212 AC: 3236 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3460

East Asian (EAS) AF: 0.0985 AC: 510 AN: 5180

South Asian (SAS) AF: 0.171 AC: 823 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4135 AN: 10542

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23495 AN: 67960

Other (OTH) AF: 0.228 AC: 480 AN: 2104

Alfa AF: 0.308 Hom.: 16610

Bravo AF: 0.220

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.72
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: rs1676536; hg19: chr11-110162430;