rs6981243

Variant names:

• chr8-53953931-C-A
• rs6981243
• NM_003702.5:c.303-145C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_003702.5(RGS20):​c.303-145C>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_003702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	NM_003702.5	MANE Select	c.303-145C>A		intron	N/A	NP_003693.2
	RGS20	NM_170587.4		c.744-145C>A		intron	N/A	NP_733466.1	O76081-1
	RGS20	NM_001286673.2		c.399-145C>A		intron	N/A	NP_001273602.1	O76081-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS20	ENST00000276500.5	TSL:1 MANE Select	c.303-145C>A		intron	N/A	ENSP00000276500.4	O76081-6
	RGS20	ENST00000297313.8	TSL:1	c.744-145C>A		intron	N/A	ENSP00000297313.3	O76081-1
	RGS20	ENST00000344277.10	TSL:1	c.399-145C>A		intron	N/A	ENSP00000344630.6	O76081-2

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

African (AFR) AF: 0.410 AC: 5425 AN: 13232

American (AMR) AF: 0.620 AC: 12537 AN: 20234

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 9762 AN: 17626

East Asian (EAS) AF: 0.789 AC: 24916 AN: 31594

South Asian (SAS) AF: 0.691 AC: 37308 AN: 53988

European-Finnish (FIN) AF: 0.601 AC: 26942 AN: 44820

Middle Eastern (MID) AF: 0.616 AC: 2354 AN: 3822

European-Non Finnish (NFE) AF: 0.588 AC: 185288 AN: 315370

Other (OTH) AF: 0.607 AC: 17450 AN: 28766

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

African (AFR) AF: 0.416 AC: 17221 AN: 41444

American (AMR) AF: 0.598 AC: 9141 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4377 AN: 5174

South Asian (SAS) AF: 0.688 AC: 3315 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6473 AN: 10564

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39880 AN: 67982

Other (OTH) AF: 0.595 AC: 1256 AN: 2110

Alfa AF: 0.572 Hom.: 55698

Bravo AF: 0.548

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.051
DANN	Benign	0.47
PhyloP100		-2.5
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: rs6981243; hg19: chr8-54866491; COSMIC: COSV52014938;