rs7736948

chr5-95807977-A-Gchr5-95807977-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 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+8530T>C		intron_variant		4		P1
RHOBTB3	ENST00000513091.1	c.45-15860A>G		intron_variant		3
GLRX	ENST00000507605.1	n.202+8530T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.799

Alfa AF: 0.784 Hom.: 76762

Bravo AF: 0.795

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.22
Dann	Benign	0.27

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: rs7736948; hg19: chr5-95143681; COSMIC: COSV72667402;