5-95804555-C-T

Position:

• chr5-95804555-C-T

Variant summary

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

The ENST00000513091.1(RHOBTB3):​c.43+15697C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,122 control chromosomes in the GnomAD database, including 1,625 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 0.13 (1625 hom., cov: 32)
• Consequence: RHOBTB3 ENST00000513091.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.95804555C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000508780.5	c.*6+11952G>A		intron_variant		4		ENSP00000422708.1
RHOBTB3	ENST00000513091.1	c.43+15697C>T		intron_variant		3		ENSP00000425342.1
GLRX	ENST00000507605.1	n.202+11952G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20117 AN: 152004 Hom.: 1621 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.132 AC: 20150 AN: 152122 Hom.: 1625 Cov.: 32 AF XY: 0.132 AC XY: 9818 AN XY: 74370

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0910 Hom.: 226

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.62

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: rs7700813; hg19: chr5-95140259;