8-53943120-T-C

Variant summary

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

The NM_170587.4(RGS20):c.659+3396T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,060 control chromosomes in the GnomAD database, including 10,651 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 0.37 (10651 hom., cov: 32)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS20	NM_170587.4	c.659+3396T>C		intron_variant		ENST00000297313.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS20	ENST00000297313.8	c.659+3396T>C		intron_variant		1	NM_170587.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56211 AN: 151944 Hom.: 10642 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.370 AC: 56256 AN: 152060 Hom.: 10651 Cov.: 32 AF XY: 0.377 AC XY: 28029 AN XY: 74332

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.342

Alfa AF: 0.345 Hom.: 8486

Bravo AF: 0.352

Asia WGS AF: 0.444 AC: 1543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.70
Dann	Benign	0.69

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: rs9298496; hg19: chr8-54855680;