dbSNP rs2074647: RGS6:c.*3G>A (chr14-72562470-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370275.1(RGS6):c.1543G>A(p.Val515Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 1,612,136 control chromosomes in the GnomAD database, including 6,778 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 838 hom., cov: 32)

Exomes 𝑓: 0.088 ( 5940 hom. )

Consequence

RGS6
NM_001370275.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

RGS6 links:

ENSG00000258871 (HGNC:):

ENSG00000258871 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016974509).

BP6

Variant 14-72562470-G-A is Benign according to our data. Variant chr14-72562470-G-A is described in ClinVar as [Benign]. Clinvar id is 1258962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2 link	c.*3G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000553525.6	NP_001191353.1	P49758-3Q2M3K2B7Z2A0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6 link	c.*3G>A		3_prime_UTR_variant	Exon 18 of 18	2	NM_001204424.2	ENSP00000451030.1		P49758-3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15434

AN:

152178

Hom.:

837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0907

Gnomad EAS

AF:

0.0651

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0544

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.0913

GnomAD3 exomes

AF:

0.0902

AC:

22398

AN:

248360

Hom.:

1078

AF XY:

0.0911

AC XY:

12265

AN XY:

134602

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0872

Gnomad ASJ exome

AF:

0.0880

Gnomad EAS exome

AF:

0.0609

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0526

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0876

AC:

127881

AN:

1459840

Hom.:

5940

Cov.:

AF XY:

0.0887

AC XY:

64404

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0888

Gnomad4 ASJ exome

AF:

0.0878

Gnomad4 EAS exome

AF:

0.0864

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0571

Gnomad4 NFE exome

AF:

0.0855

Gnomad4 OTH exome

AF:

0.0939

GnomAD4 genome

AF:

0.101

AC:

15448

AN:

152296

Hom.:

838

Cov.:

AF XY:

0.0996

AC XY:

7420

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0907

Gnomad4 EAS

AF:

0.0649

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0544

Gnomad4 NFE

AF:

0.0902

Gnomad4 OTH

AF:

0.0913

Alfa

AF:

0.0921

Hom.:

1067

Bravo

AF:

0.106

TwinsUK

AF:

0.0871

AC:

323

ALSPAC

AF:

0.0799

AC:

308

ESP6500AA

AF:

0.140

AC:

619

ESP6500EA

AF:

0.0917

AC:

789

ExAC

AF:

0.0922

AC:

11193

Asia WGS

AF:

0.0960

AC:

337

AN:

3478

EpiCase

AF:

0.0987

EpiControl

AF:

0.0996

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15375002) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0017

GERP RS

3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over