rs11135434

chr5-95807894-C-T

Variant summary

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

The ENST00000508780.5(GLRX):c.*6+8613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,030 control chromosomes in the GnomAD database, including 21,072 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 0.52 (21072 hom., cov: 32)
• Consequence: GLRX ENST00000508780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

Genes affected

GLRX (HGNC:4330): (glutaredoxin) This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer's disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2011]

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 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
GLRX	ENST00000508780.5	c.*6+8613G>A		intron_variant		4		P1
RHOBTB3	ENST00000513091.1	c.45-15943C>T		intron_variant		3
GLRX	ENST00000507605.1	n.202+8613G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79661 AN: 151910 Hom.: 21052 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.524 AC: 79734 AN: 152030 Hom.: 21072 Cov.: 32 AF XY: 0.519 AC XY: 38563 AN XY: 74320

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.555

Alfa AF: 0.555 Hom.: 48848

Bravo AF: 0.520

Asia WGS AF: 0.450 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.77
Dann	Benign	0.63

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: rs11135434; hg19: chr5-95143598; COSMIC: COSV72667401;