ENST00000508780.5:c.*6+8613G>A

Variant names:

• chr5-95807894-C-T
• rs11135434
• ENST00000508780.5:c.*6+8613G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX	ENST00000508780.5	TSL:4	c.*6+8613G>A		intron	N/A	ENSP00000422708.1
	GLRX	ENST00000958151.1		c.*6+8613G>A		intron	N/A	ENSP00000628210.1
	RHOBTB3	ENST00000513091.1	TSL:3	c.44-15943C>T		intron	N/A	ENSP00000425342.1

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

African (AFR) AF: 0.508 AC: 21060 AN: 41456

American (AMR) AF: 0.480 AC: 7340 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2083 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5170

South Asian (SAS) AF: 0.467 AC: 2250 AN: 4822

European-Finnish (FIN) AF: 0.504 AC: 5316 AN: 10546

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.560 AC: 38028 AN: 67956

Other (OTH) AF: 0.555 AC: 1173 AN: 2114

Alfa AF: 0.548 Hom.: 101467

Bravo AF: 0.520

Asia WGS AF: 0.450 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.63
PhyloP100		-0.47
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: rs11135434; hg19: chr5-95143598; COSMIC: COSV72667401;