chr8-100012277-A-C

Position:

• chr8-100012277-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015668.5(RGS22):​c.2167-3708T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,924 control chromosomes in the GnomAD database, including 3,069 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 0.19 (3069 hom., cov: 31)
• Consequence: RGS22 NM_015668.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS22	NM_015668.5	c.2167-3708T>G		intron_variant		ENST00000360863.11	NP_056483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000360863.11	c.2167-3708T>G		intron_variant		1	NM_015668.5	ENSP00000354109	P3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29315 AN: 151806 Hom.: 3070 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.193 AC: 29329 AN: 151924 Hom.: 3069 Cov.: 31 AF XY: 0.194 AC XY: 14392 AN XY: 74258

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.168

Alfa AF: 0.158 Hom.: 4128

Bravo AF: 0.188

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs7006527; hg19: chr8-101024505;