chr5-95804555-C-T

Variant names:

• chr5-95804555-C-T
• rs7700813
• ENST00000508780.5:c.*6+11952G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513091.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX	ENST00000508780.5	TSL:4	c.*6+11952G>A		intron	N/A	ENSP00000422708.1	P35754
	GLRX	ENST00000958151.1		c.*6+11952G>A		intron	N/A	ENSP00000628210.1
	RHOBTB3	ENST00000513091.1	TSL:3	c.43+15697C>T		intron	N/A	ENSP00000425342.1	H0Y9W9

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

African (AFR) AF: 0.221 AC: 9149 AN: 41464

American (AMR) AF: 0.0970 AC: 1482 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3466

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4826

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10578

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.106 AC: 7222 AN: 68002

Other (OTH) AF: 0.130 AC: 275 AN: 2108

Alfa AF: 0.120 Hom.: 730

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.62
PhyloP100		-0.66
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7700813;

hg19: chr5-95140259;