rs7736948

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-95807977-A-G
• chr5-95807977-A-T

Variant summary

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

The ENST00000513091.1(RHOBTB3):​c.44-15860A>G 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: RHOBTB3 ENST00000513091.1 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000508780.5	c.*6+8530T>C		intron_variant	Intron 2 of 2	4		ENSP00000422708.1
RHOBTB3	ENST00000513091.1	c.44-15860A>G		intron_variant	Intron 1 of 1	3		ENSP00000425342.1
GLRX	ENST00000507605.1	n.202+8530T>C		intron_variant	Intron 2 of 3	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;