chr8-100127185-G-A

Position:

• chr8-100127185-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000520117.5	c.33+3947C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.612

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2453628; hg19: chr8-101139413;