chr5-95777162-T-C

Variant names:

• chr5-95777162-T-C
• rs3777218
• NM_014899.4:c.1283-3090T>C

Variant summary

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

The NM_014899.4(RHOBTB3):​c.1283-3090T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,038 control chromosomes in the GnomAD database, including 19,325 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 0.50 (19325 hom., cov: 32)
• Consequence: RHOBTB3 NM_014899.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 7 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014899.4. 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
	RHOBTB3	NM_014899.4	MANE Select	c.1283-3090T>C		intron	N/A	NP_055714.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB3	ENST00000379982.8	TSL:1 MANE Select	c.1283-3090T>C		intron	N/A	ENSP00000369318.3
	RHOBTB3	ENST00000890088.1		c.914-3090T>C		intron	N/A	ENSP00000560147.1
	RHOBTB3	ENST00000958070.1		c.917-3234T>C		intron	N/A	ENSP00000628129.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76329 AN: 151920 Hom.: 19307 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.502 AC: 76399 AN: 152038 Hom.: 19325 Cov.: 32 AF XY: 0.496 AC XY: 36841 AN XY: 74296

African (AFR) AF: 0.501 AC: 20785 AN: 41480

American (AMR) AF: 0.447 AC: 6820 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1868 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1639 AN: 5184

South Asian (SAS) AF: 0.553 AC: 2667 AN: 4826

European-Finnish (FIN) AF: 0.511 AC: 5381 AN: 10536

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35524 AN: 67960

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.517 Hom.: 36632

Bravo AF: 0.500

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		-0.23
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: rs3777218; hg19: chr5-95112866;