ENST00000508780.5:c.*6+8530T>C

Variant names:

• chr5-95807977-A-G
• rs7736948
• ENST00000508780.5:c.*6+8530T>C

Variant summary

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

The ENST00000508780.5(GLRX):​c.*6+8530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,264 control chromosomes in the GnomAD database, including 48,991 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 0.80 (48991 hom., cov: 33)
• Consequence: GLRX ENST00000508780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX	ENST00000508780.5	TSL:4	c.*6+8530T>C		intron	N/A	ENSP00000422708.1
	RHOBTB3	ENST00000513091.1	TSL:3	c.44-15860A>G		intron	N/A	ENSP00000425342.1
	GLRX	ENST00000507605.1	TSL:2	n.202+8530T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.795 AC: 121005 AN: 152146 Hom.: 48931 Cov.: 33

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.801

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

GnomAD4 genome AF: 0.795 AC: 121125 AN: 152264 Hom.: 48991 Cov.: 33 AF XY: 0.788 AC XY: 58642 AN XY: 74446

African (AFR) AF: 0.914 AC: 37987 AN: 41580

American (AMR) AF: 0.702 AC: 10735 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2785 AN: 3472

East Asian (EAS) AF: 0.416 AC: 2161 AN: 5190

South Asian (SAS) AF: 0.765 AC: 3695 AN: 4828

European-Finnish (FIN) AF: 0.715 AC: 7560 AN: 10576

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53618 AN: 68004

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.787 Hom.: 181598

Bravo AF: 0.795

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.27
PhyloP100		-1.3
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: rs7736948; hg19: chr5-95143681; COSMIC: COSV72667402;