Genetic Variant ENST00000374134.7:c.-413G>A (chr9-113580764-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000374134.7(RGS3):c.-413G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 981,102 control chromosomes in the GnomAD database, including 5,222 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 0.12 ( 1281 hom., cov: 33)

Exomes 𝑓: 0.095 ( 3941 hom. )

Consequence

RGS3
ENST00000374134.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.641

Publications

13 publications found

Variant links:

Genes affected

RGS3 (HGNC:9999): (regulator of G protein signaling 3) This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear. [provided by RefSeq, Jan 2013]

RGS3 links:

ENSG00000237073 (HGNC:58614):

ENSG00000237073 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS3	NM_001394167.1 link	c.1702-2686G>A		intron_variant	Intron 17 of 22	ENST00000695401.1	NP_001381096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS3	ENST00000695401.1 link	c.1702-2686G>A		intron_variant	Intron 17 of 22		NM_001394167.1	ENSP00000511882.1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17981

AN:

152162

Hom.:

1265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0620

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0974

Gnomad OTH

AF:

0.0904

GnomAD4 exome

AF:

0.0946

AC:

78421

AN:

828822

Hom.:

3941

Cov.:

AF XY:

0.0937

AC XY:

35884

AN XY:

382992

show subpopulations

African (AFR)

AF:

0.197

AC:

3096

AN:

15686

American (AMR)

AF:

0.0440

AC:

AN:

978

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

286

AN:

5120

East Asian (EAS)

AF:

0.000550

AC:

AN:

3636

South Asian (SAS)

AF:

0.0435

AC:

713

AN:

16376

European-Finnish (FIN)

AF:

0.160

AC:

AN:

306

Middle Eastern (MID)

AF:

0.0665

AC:

107

AN:

1610

European-Non Finnish (NFE)

AF:

0.0949

AC:

71899

AN:

757928

Other (OTH)

AF:

0.0819

AC:

2226

AN:

27182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3363

6726

10090

13453

16816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3658

7316

10974

14632

18290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.118

AC:

18043

AN:

152280

Hom.:

1281

Cov.:

AF XY:

0.118

AC XY:

8805

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.190

AC:

7878

AN:

41550

American (AMR)

AF:

0.0619

AC:

947

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

253

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0416

AC:

201

AN:

4828

European-Finnish (FIN)

AF:

0.181

AC:

1913

AN:

10598

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0974

AC:

6627

AN:

68024

Other (OTH)

AF:

0.0895

AC:

189

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

810

1620

2429

3239

4049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0954

Hom.:

1147

Bravo

AF:

0.112

Asia WGS

AF:

0.0340

AC:

121

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.3

(source)

DANN

Benign

0.86

PhyloP100

-0.64

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over