8-100106516-G-C

Variant names:

• chr8-100106516-G-C
• rs2453627
• ENST00000517828.5:c.49-13007C>G

Variant summary

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

The ENST00000517828.5(RGS22):​c.49-13007C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,076 control chromosomes in the GnomAD database, including 15,461 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 0.44 (15461 hom., cov: 32)
• Consequence: RGS22 ENST00000517828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517828.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	ENST00000517828.5	TSL:3	c.49-13007C>G		intron	N/A	ENSP00000427754.1	E5RGJ7
	RGS22	ENST00000520117.5	TSL:3	c.34-13007C>G		intron	N/A	ENSP00000429198.1	E5RJ23
	RGS22	ENST00000519408.5	TSL:4	c.-517C>G		upstream_gene	N/A	ENSP00000427930.1	E5RFV6

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67014 AN: 151958 Hom.: 15445 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.441 AC: 67067 AN: 152076 Hom.: 15461 Cov.: 32 AF XY: 0.442 AC XY: 32872 AN XY: 74324

African (AFR) AF: 0.552 AC: 22900 AN: 41514

American (AMR) AF: 0.503 AC: 7694 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2615 AN: 5138

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4824

European-Finnish (FIN) AF: 0.407 AC: 4297 AN: 10568

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25525 AN: 67962

Other (OTH) AF: 0.406 AC: 854 AN: 2104

Alfa AF: 0.402 Hom.: 1580

Bravo AF: 0.456

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.39
PhyloP100		-2.6
PromoterAI		-0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2453627; hg19: chr8-101118744;