5-95818506-C-G

Variant names:

• chr5-95818506-C-G
• rs3822751
• NM_001118890.2:c.208-1880G>C

Variant summary

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

The NM_001118890.2(GLRX):​c.208-1880G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,986 control chromosomes in the GnomAD database, including 10,053 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 (10051 hom., cov: 31)
  • Exomes 𝑓: 0.26 (2 hom.)
• Consequence: GLRX NM_001118890.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX	NM_001118890.2	c.208-1880G>C		intron_variant	Intron 1 of 2	ENST00000237858.11	NP_001112362.1
GLRX	NM_001243658.2	c.208-1880G>C		intron_variant	Intron 1 of 2		NP_001230587.1
GLRX	NM_001243659.2	c.208-1880G>C		intron_variant	Intron 1 of 2		NP_001230588.1
GLRX	NM_002064.3	c.208-1880G>C		intron_variant	Intron 1 of 2		NP_002055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000237858.11	c.208-1880G>C		intron_variant	Intron 1 of 2	1	NM_001118890.2	ENSP00000237858.6

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51715 AN: 151810 Hom.: 10035 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.259 AC: 15 AN: 58 Hom.: 2 Cov.: 0 AF XY: 0.281 AC XY: 9 AN XY: 32

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.286

GnomAD4 genome AF: 0.341 AC: 51786 AN: 151928 Hom.: 10051 Cov.: 31 AF XY: 0.344 AC XY: 25532 AN XY: 74280

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.309

Alfa AF: 0.0966 Hom.: 121

Bravo AF: 0.357

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.30

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: rs3822751; hg19: chr5-95154210;