8-100125669-T-C

Variant names:

• chr8-100125669-T-C
• rs2453626
• ENST00000517828.5:c.48+82A>G

Variant summary

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

The ENST00000517828.5(RGS22):​c.48+82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 455,934 control chromosomes in the GnomAD database, including 79,899 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 (28310 hom., cov: 31)
  • Exomes 𝑓: 0.58 (51589 hom.)
• Consequence: RGS22 ENST00000517828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 16 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 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.48+82A>G		intron	N/A	ENSP00000427754.1	E5RGJ7
	RGS22	ENST00000520117.5	TSL:3	c.33+5463A>G		intron	N/A	ENSP00000429198.1	E5RJ23

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92030 AN: 151854 Hom.: 28288 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.577 AC: 175512 AN: 303962 Hom.: 51589 AF XY: 0.572 AC XY: 99032 AN XY: 173072

African (AFR) AF: 0.696 AC: 6009 AN: 8628

American (AMR) AF: 0.723 AC: 19724 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 6059 AN: 10790

East Asian (EAS) AF: 0.607 AC: 5587 AN: 9210

South Asian (SAS) AF: 0.563 AC: 33643 AN: 59744

European-Finnish (FIN) AF: 0.585 AC: 7239 AN: 12364

Middle Eastern (MID) AF: 0.646 AC: 1797 AN: 2782

European-Non Finnish (NFE) AF: 0.550 AC: 87417 AN: 158932

Other (OTH) AF: 0.565 AC: 8037 AN: 14230

GnomAD4 genome AF: 0.606 AC: 92090 AN: 151972 Hom.: 28310 Cov.: 31 AF XY: 0.608 AC XY: 45156 AN XY: 74274

African (AFR) AF: 0.695 AC: 28801 AN: 41444

American (AMR) AF: 0.662 AC: 10110 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1986 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3241 AN: 5160

South Asian (SAS) AF: 0.540 AC: 2603 AN: 4820

European-Finnish (FIN) AF: 0.585 AC: 6165 AN: 10546

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37343 AN: 67944

Other (OTH) AF: 0.590 AC: 1247 AN: 2112

Alfa AF: 0.571 Hom.: 40942

Bravo AF: 0.617

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.20
PhyloP100		-2.8
PromoterAI		0.012	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2453626; hg19: chr8-101137897;