chr8-100127185-G-A

Variant names:

• chr8-100127185-G-A
• rs2453628
• ENST00000520117.5:c.33+3947C>T

Variant summary

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

The ENST00000520117.5(RGS22):​c.33+3947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,128 control chromosomes in the GnomAD database, including 32,515 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 0.64 (32515 hom., cov: 32)
• Consequence: RGS22 ENST00000520117.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000520117.5	c.33+3947C>T		intron_variant	Intron 1 of 4	3		ENSP00000429198.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97301 AN: 152010 Hom.: 32479 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.640 AC: 97385 AN: 152128 Hom.: 32515 Cov.: 32 AF XY: 0.642 AC XY: 47705 AN XY: 74348

African (AFR) AF: 0.831 AC: 34513 AN: 41526

American (AMR) AF: 0.673 AC: 10302 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3470

East Asian (EAS) AF: 0.700 AC: 3621 AN: 5172

South Asian (SAS) AF: 0.568 AC: 2737 AN: 4822

European-Finnish (FIN) AF: 0.569 AC: 5997 AN: 10542

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36350 AN: 67990

Other (OTH) AF: 0.612 AC: 1290 AN: 2108

Alfa AF: 0.598 Hom.: 4138

Bravo AF: 0.657

Asia WGS AF: 0.631 AC: 2196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.19
PhyloP100		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2453628; hg19: chr8-101139413;