ENST00000508780.5:c.*6+11641C>T

Variant names:

• chr5-95804866-G-A
• rs13173742
• ENST00000508780.5:c.*6+11641C>T

Variant summary

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

The ENST00000508780.5(GLRX):​c.*6+11641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,990 control chromosomes in the GnomAD database, including 9,116 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 0.34 (9116 hom., cov: 32)
• Consequence: GLRX ENST00000508780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000508780.5	c.*6+11641C>T		intron_variant	Intron 2 of 2	4		ENSP00000422708.1
RHOBTB3	ENST00000513091.1	c.43+16008G>A		intron_variant	Intron 1 of 1	3		ENSP00000425342.1
GLRX	ENST00000507605.1	n.202+11641C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51277 AN: 151872 Hom.: 9109 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.338 AC: 51312 AN: 151990 Hom.: 9116 Cov.: 32 AF XY: 0.334 AC XY: 24780 AN XY: 74276

African (AFR) AF: 0.217 AC: 9000 AN: 41452

American (AMR) AF: 0.349 AC: 5332 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1223 AN: 5180

South Asian (SAS) AF: 0.378 AC: 1817 AN: 4806

European-Finnish (FIN) AF: 0.346 AC: 3647 AN: 10548

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27627 AN: 67940

Other (OTH) AF: 0.367 AC: 773 AN: 2104

Alfa AF: 0.382 Hom.: 10504

Bravo AF: 0.333

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.66
PhyloP100		-1.1
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: rs13173742; hg19: chr5-95140570; COSMIC: COSV72667395;