chr8-53931053-C-G

Variant names:

• chr8-53931053-C-G
• rs2128821
• NM_003702.5:c.70-8523C>G

Variant summary

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

The NM_003702.5(RGS20):​c.70-8523C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,910 control chromosomes in the GnomAD database, including 10,818 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 0.35 (10818 hom., cov: 31)
• Consequence: RGS20 NM_003702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003702.5. 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
	RGS20	NM_003702.5	MANE Select	c.70-8523C>G		intron	N/A	NP_003693.2
	RGS20	NM_170587.4		c.511-8523C>G		intron	N/A	NP_733466.1
	RGS20	NM_001286673.2		c.166-8523C>G		intron	N/A	NP_001273602.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	ENST00000276500.5	TSL:1 MANE Select	c.70-8523C>G		intron	N/A	ENSP00000276500.4
	RGS20	ENST00000297313.8	TSL:1	c.511-8523C>G		intron	N/A	ENSP00000297313.3
	RGS20	ENST00000344277.10	TSL:1	c.166-8523C>G		intron	N/A	ENSP00000344630.6

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53835 AN: 151792 Hom.: 10803 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.355 AC: 53889 AN: 151910 Hom.: 10818 Cov.: 31 AF XY: 0.356 AC XY: 26441 AN XY: 74260

African (AFR) AF: 0.558 AC: 23125 AN: 41406

American (AMR) AF: 0.208 AC: 3175 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1563 AN: 5164

South Asian (SAS) AF: 0.360 AC: 1728 AN: 4806

European-Finnish (FIN) AF: 0.328 AC: 3465 AN: 10554

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19018 AN: 67952

Other (OTH) AF: 0.309 AC: 649 AN: 2098

Alfa AF: 0.165 Hom.: 302

Bravo AF: 0.353

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.54
PhyloP100		0.26
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: rs2128821; hg19: chr8-54843613;