rs4734443

Variant names:

• chr8-100000193-C-T
• rs4734443
• NM_015668.5:c.2791-773G>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.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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	NM_015668.5	MANE Select	c.2791-773G>A		intron	N/A	NP_056483.3
	RGS22	NM_001286692.2		c.2755-773G>A		intron	N/A	NP_001273621.1
	RGS22	NM_001286693.2		c.2248-773G>A		intron	N/A	NP_001273622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	ENST00000360863.11	TSL:1 MANE Select	c.2791-773G>A		intron	N/A	ENSP00000354109.6
	RGS22	ENST00000523437.5	TSL:1	c.2755-773G>A		intron	N/A	ENSP00000428212.1
	RGS22	ENST00000523287.5	TSL:2	c.2248-773G>A		intron	N/A	ENSP00000429382.1

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

African (AFR) AF: 0.162 AC: 6717 AN: 41442

American (AMR) AF: 0.447 AC: 6823 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2319 AN: 5166

South Asian (SAS) AF: 0.327 AC: 1576 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4920 AN: 10534

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27569 AN: 67928

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.389 Hom.: 18808

Bravo AF: 0.335

Asia WGS AF: 0.393 AC: 1368 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.36
PhyloP100		0.25
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: rs4734443; hg19: chr8-101012421;