rs3133679

Variant names:

• chr8-100013770-C-T
• rs3133679
• NM_015668.5:c.2167-5201G>A

Variant summary

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

The NM_015668.5(RGS22):​c.2167-5201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,924 control chromosomes in the GnomAD database, including 28,390 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 0.61 (28390 hom., cov: 31)
• Consequence: RGS22 NM_015668.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 2 publications found

Genes affected

RGS22 (HGNC:24499): (regulator of G protein signaling 22) Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015668.5. 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
	RGS22	NM_015668.5	MANE Select	c.2167-5201G>A		intron	N/A	NP_056483.3	Q8NE09-1
	RGS22	NM_001286692.2		c.2131-5201G>A		intron	N/A	NP_001273621.1	Q8NE09-3
	RGS22	NM_001286693.2		c.1624-5201G>A		intron	N/A	NP_001273622.1	G3V112

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	ENST00000360863.11	TSL:1 MANE Select	c.2167-5201G>A		intron	N/A	ENSP00000354109.6	Q8NE09-1
	RGS22	ENST00000523437.5	TSL:1	c.2131-5201G>A		intron	N/A	ENSP00000428212.1	Q8NE09-3
	RGS22	ENST00000519725.5	TSL:1	n.*742-5201G>A		intron	N/A	ENSP00000427798.1	Q8NE09-2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92523 AN: 151806 Hom.: 28356 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.610 AC: 92600 AN: 151924 Hom.: 28390 Cov.: 31 AF XY: 0.616 AC XY: 45726 AN XY: 74262

African (AFR) AF: 0.636 AC: 26337 AN: 41410

American (AMR) AF: 0.660 AC: 10083 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3194 AN: 5144

South Asian (SAS) AF: 0.592 AC: 2847 AN: 4812

European-Finnish (FIN) AF: 0.696 AC: 7346 AN: 10560

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39020 AN: 67942

Other (OTH) AF: 0.584 AC: 1234 AN: 2114

Alfa AF: 0.585 Hom.: 13900

Bravo AF: 0.607

Asia WGS AF: 0.632 AC: 2195 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.050
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: rs3133679; hg19: chr8-101025998;