8-100125669-T-C

Position:

• chr8-100125669-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.100125669T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000517828.5	c.48+82A>G		intron_variant		3		ENSP00000427754.1
RGS22	ENST00000520117.5	c.33+5463A>G		intron_variant		3		ENSP00000429198.1

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

Gnomad4 AFR exome AF: 0.696

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.565

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

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.590

Alfa AF: 0.564 Hom.: 31264

Bravo AF: 0.617

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2453626; hg19: chr8-101137897;