rs6011280

Positions:

• chr20-64073787-A-C
• chr20-64073787-A-G

Variant summary

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

The NM_005873.3(RGS19):​c.*66T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,422,218 control chromosomes in the GnomAD database, including 83,723 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 0.36 (9864 hom., cov: 34)
  • Exomes 𝑓: 0.34 (73859 hom.)
• Consequence: RGS19 NM_005873.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

RGS19 (HGNC:13735): (regulator of G protein signaling 19) G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS19	NM_005873.3	c.*66T>G		3_prime_UTR_variant	6/6	ENST00000395042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS19	ENST00000395042.2	c.*66T>G		3_prime_UTR_variant	6/6	1	NM_005873.3	P1
RGS19	ENST00000332298.9	c.*66T>G		3_prime_UTR_variant	6/6	1		P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53934 AN: 152022 Hom.: 9830 Cov.: 34

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.337 AC: 428095 AN: 1270078 Hom.: 73859 Cov.: 19 AF XY: 0.343 AC XY: 215881 AN XY: 629414

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.355 AC: 54030 AN: 152140 Hom.: 9864 Cov.: 34 AF XY: 0.355 AC XY: 26434 AN XY: 74384

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.369

Alfa AF: 0.343 Hom.: 11170

Bravo AF: 0.359

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.44

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: rs6011280; hg19: chr20-62705140; COSMIC: COSV58659790; COSMIC: COSV58659790;