rs13173742

Positions:

• chr5-95804866-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRX	ENST00000508780.5	c.*6+11641C>T		intron_variant		4		P1
RHOBTB3	ENST00000513091.1	c.44+16008G>A		intron_variant		3
GLRX	ENST00000507605.1	n.202+11641C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.367

Alfa AF: 0.388 Hom.: 6583

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

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: rs13173742; hg19: chr5-95140570; COSMIC: COSV72667395;