8-53931053-C-G

Position:

• chr8-53931053-C-G

Variant summary

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

The NM_170587.4(RGS20):​c.511-8523C>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_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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]

RGS20 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS20	NM_170587.4	c.511-8523C>G		intron_variant		ENST00000297313.8	NP_733466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.511-8523C>G		intron_variant		1	NM_170587.4	ENSP00000297313.3
RGS20	ENST00000276500.4	c.70-8523C>G		intron_variant		1		ENSP00000276500.4

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

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.309

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.54

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: rs2128821; hg19: chr8-54843613;