rs4734443

Positions:

• chr8-100000193-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.2791-773G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,926 control chromosomes in the GnomAD database, including 10,055 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 0.34 (10055 hom., cov: 31)
• Consequence: RGS22 NM_015668.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS22	NM_015668.5	c.2791-773G>A		intron_variant		ENST00000360863.11	NP_056483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000360863.11	c.2791-773G>A		intron_variant		1	NM_015668.5	ENSP00000354109	P3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52209 AN: 151808 Hom.: 10050 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.344 AC: 52225 AN: 151926 Hom.: 10055 Cov.: 31 AF XY: 0.348 AC XY: 25864 AN XY: 74260

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.331

Alfa AF: 0.391 Hom.: 16192

Bravo AF: 0.335

Asia WGS AF: 0.393 AC: 1368 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.36

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: rs4734443; hg19: chr8-101012421;