rs3133679

Positions:

• chr8-100013770-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS22	NM_015668.5	c.2167-5201G>A		intron_variant		ENST00000360863.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000360863.11	c.2167-5201G>A		intron_variant		1	NM_015668.5	P3

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

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.584

Alfa AF: 0.587 Hom.: 12525

Bravo AF: 0.607

Asia WGS AF: 0.632 AC: 2195 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.1
DANN	Benign	0.59

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: rs3133679; hg19: chr8-101025998;