8-53867649-C-T

Variant names:

• chr8-53867649-C-T
• rs1466525
• ENST00000297313.8:c.166-11609C>T

Variant summary

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

The NM_170587.4(RGS20):​c.166-11609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 151,526 control chromosomes in the GnomAD database, including 53,928 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 0.84 (53928 hom., cov: 29)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 4 publications found

Genes affected

RGS20 (HGNC:14600): (regulator of G protein signaling 20) The protein encoded by this gene belongs to the family of regulator of G protein signaling (RGS) proteins, which are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound forms. This protein selectively binds to G(z)-alpha and G(alpha)-i2 subunits, and regulates their signaling activities. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000302028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170587.4. 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
	RGS20	NM_170587.4		c.166-11609C>T		intron	N/A	NP_733466.1	O76081-1
	RGS20	NM_001286673.2		c.165+15585C>T		intron	N/A	NP_001273602.1	O76081-2
	RGS20	NM_001286675.2		c.35+15585C>T		intron	N/A	NP_001273604.1	O76081-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	ENST00000297313.8	TSL:1	c.166-11609C>T		intron	N/A	ENSP00000297313.3	O76081-1
	RGS20	ENST00000344277.10	TSL:1	c.165+15585C>T		intron	N/A	ENSP00000344630.6	O76081-2
	RGS20	ENST00000517659.5	TSL:1	n.165+15585C>T		intron	N/A	ENSP00000428795.1	E5RGA3

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127221 AN: 151408 Hom.: 53873 Cov.: 29

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.840 AC: 127332 AN: 151526 Hom.: 53928 Cov.: 29 AF XY: 0.837 AC XY: 61928 AN XY: 74024

African (AFR) AF: 0.958 AC: 39681 AN: 41408

American (AMR) AF: 0.857 AC: 13018 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2541 AN: 3446

East Asian (EAS) AF: 0.879 AC: 4534 AN: 5160

South Asian (SAS) AF: 0.720 AC: 3431 AN: 4766

European-Finnish (FIN) AF: 0.757 AC: 7882 AN: 10418

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53448 AN: 67828

Other (OTH) AF: 0.850 AC: 1784 AN: 2100

Alfa AF: 0.801 Hom.: 57408

Bravo AF: 0.855

Asia WGS AF: 0.840 AC: 2917 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.77
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs1466525; hg19: chr8-54780209;