rs6981243

Positions:

• chr8-53953931-C-A
• chr8-53953931-C-G
• chr8-53953931-C-T

Variant summary

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

The NM_170587.4(RGS20):​c.744-145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 681,498 control chromosomes in the GnomAD database, including 123,725 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 0.55 (24229 hom., cov: 32)
  • Exomes 𝑓: 0.61 (99496 hom.)
• Consequence: RGS20 NM_170587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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 (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS20	NM_170587.4	c.744-145C>A		intron_variant		ENST00000297313.8	NP_733466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS20	ENST00000297313.8	c.744-145C>A		intron_variant		1	NM_170587.4	ENSP00000297313

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84319 AN: 151928 Hom.: 24217 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.608 AC: 321982 AN: 529452 Hom.: 99496 AF XY: 0.612 AC XY: 175318 AN XY: 286432

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.555 AC: 84368 AN: 152046 Hom.: 24229 Cov.: 32 AF XY: 0.561 AC XY: 41697 AN XY: 74348

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.595

Alfa AF: 0.575 Hom.: 32984

Bravo AF: 0.548

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.051
DANN	Benign	0.47

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: rs6981243; hg19: chr8-54866491; COSMIC: COSV52014938;