rs2233802

Variant names:

• chr9-19049598-C-A
• rs2233802
• NM_006570.5:c.-62C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-19049598-C-A
• chr9-19049598-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006570.5(RRAGA):​c.-62C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,307,996 control chromosomes in the GnomAD database, including 20,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5183 hom., cov: 33)
  • Exomes 𝑓: 0.15 (15556 hom.)
• Consequence: RRAGA NM_006570.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.198
• Publications: 9 publications found

Genes affected

RRAGA (HGNC:16963): (Ras related GTP binding A) Enables several functions, including GTP binding activity; protein dimerization activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular response to amino acid starvation; negative regulation of autophagy; and positive regulation of TORC1 signaling. Located in lysosome and nucleus. Colocalizes with GATOR1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SAXO1 (HGNC:28566): (stabilizer of axonemal microtubules 1) Enables microtubule binding activity. Involved in several processes, including cold acclimation; positive regulation of cilium assembly; and protein stabilization. Located in microtubule cytoskeleton and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 9-19049598-C-A is Benign according to our data. Variant chr9-19049598-C-A is described in ClinVar as Benign. ClinVar VariationId is 1269481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006570.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGA	NM_006570.5	MANE Select	c.-62C>A		5_prime_UTR	Exon 1 of 1	NP_006561.1	Q7L523

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGA	ENST00000380527.3	TSL:6 MANE Select	c.-62C>A		5_prime_UTR	Exon 1 of 1	ENSP00000369899.1	Q7L523
	SAXO1	ENST00000542071.2	TSL:3	c.-547G>T		upstream_gene	N/A	ENSP00000438823.2	F6S232
	SAXO1	ENST00000649457.1		c.-547G>T		upstream_gene	N/A	ENSP00000497677.1	F6S232

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34384 AN: 152038 Hom.: 5177 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.155 AC: 179009 AN: 1155840 Hom.: 15556 Cov.: 15 AF XY: 0.155 AC XY: 88505 AN XY: 572610

African (AFR) AF: 0.450 AC: 11785 AN: 26172

American (AMR) AF: 0.116 AC: 3110 AN: 26796

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 2922 AN: 19408

East Asian (EAS) AF: 0.0458 AC: 1597 AN: 34888

South Asian (SAS) AF: 0.155 AC: 10259 AN: 66176

European-Finnish (FIN) AF: 0.137 AC: 6106 AN: 44422

Middle Eastern (MID) AF: 0.216 AC: 1042 AN: 4826

European-Non Finnish (NFE) AF: 0.151 AC: 133591 AN: 883986

Other (OTH) AF: 0.175 AC: 8597 AN: 49166

GnomAD4 genome AF: 0.226 AC: 34424 AN: 152156 Hom.: 5183 Cov.: 33 AF XY: 0.221 AC XY: 16435 AN XY: 74392

African (AFR) AF: 0.433 AC: 17959 AN: 41478

American (AMR) AF: 0.153 AC: 2349 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.0486 AC: 251 AN: 5168

South Asian (SAS) AF: 0.145 AC: 703 AN: 4832

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10612

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10534 AN: 67980

Other (OTH) AF: 0.235 AC: 495 AN: 2110

Alfa AF: 0.212 Hom.: 577

Bravo AF: 0.238

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.83
PhyloP100		0.20
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs2233802; hg19: chr9-19049596; COSMIC: COSV107502170; COSMIC: COSV107502170;