8-100012277-A-T

Variant names:

• chr8-100012277-A-T
• rs7006527
• NM_015668.5:c.2167-3708T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015668.5(RGS22):​c.2167-3708T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
• Consequence: RGS22 NM_015668.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015668.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	NM_015668.5	MANE Select	c.2167-3708T>A		intron	N/A	NP_056483.3
	RGS22	NM_001286692.2		c.2131-3708T>A		intron	N/A	NP_001273621.1
	RGS22	NM_001286693.2		c.1624-3708T>A		intron	N/A	NP_001273622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	ENST00000360863.11	TSL:1 MANE Select	c.2167-3708T>A		intron	N/A	ENSP00000354109.6
	RGS22	ENST00000523437.5	TSL:1	c.2131-3708T>A		intron	N/A	ENSP00000428212.1
	RGS22	ENST00000519725.5	TSL:1	n.*742-3708T>A		intron	N/A	ENSP00000427798.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151858 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74162

African (AFR) AF: 0.00 AC: 0 AN: 41240

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 10005

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		0.58

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

Other links and lift over

dbSNP: rs7006527; hg19: chr8-101024505;