rs7736948

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
GLRXENST00000508780.5 linkc.*6+8530T>C intron_variant Intron 2 of 2 4 ENSP00000422708.1 P35754
RHOBTB3ENST00000513091.1 linkc.44-15860A>G intron_variant Intron 1 of 1 3 ENSP00000425342.1 H0Y9W9
GLRXENST00000507605.1 linkn.202+8530T>C intron_variant Intron 2 of 3 2

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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