Genetic Variant ENST00000488620.5:n.105C>T (chr9-113565180-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000488620.5(RGS3):n.105C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,230,526 control chromosomes in the GnomAD database, including 2,112 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 0.039 ( 158 hom., cov: 32)

Exomes 𝑓: 0.057 ( 1954 hom. )

Consequence

RGS3
ENST00000488620.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

7 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS3	NM_001394167.1 link	c.1702-18270C>T		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.1702-18270C>T		intron_variant	Intron 17 of 22		NM_001394167.1	ENSP00000511882.1		A0A8Q3WKG2

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5981

AN:

152066

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.0161

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0420

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0364

GnomAD4 exome

AF:

0.0573

AC:

61772

AN:

1078342

Hom.:

1954

Cov.:

AF XY:

0.0583

AC XY:

30495

AN XY:

522638

show subpopulations

African (AFR)

AF:

0.00759

AC:

171

AN:

22520

American (AMR)

AF:

0.0168

AC:

351

AN:

20850

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

970

AN:

11638

East Asian (EAS)

AF:

0.0139

AC:

172

AN:

12358

South Asian (SAS)

AF:

0.0957

AC:

6285

AN:

65698

European-Finnish (FIN)

AF:

0.0507

AC:

534

AN:

10524

Middle Eastern (MID)

AF:

0.0601

AC:

234

AN:

3892

European-Non Finnish (NFE)

AF:

0.0570

AC:

50808

AN:

891918

Other (OTH)

AF:

0.0577

AC:

2247

AN:

38944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

3187

6374

9562

12749

15936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2296

4592

6888

9184

11480

<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:

0.0393

AC:

5978

AN:

152184

Hom.:

158

Cov.:

AF XY:

0.0389

AC XY:

2891

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.00915

AC:

380

AN:

41538

American (AMR)

AF:

0.0214

AC:

328

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

313

AN:

3472

East Asian (EAS)

AF:

0.0161

AC:

AN:

5152

South Asian (SAS)

AF:

0.100

AC:

483

AN:

4814

European-Finnish (FIN)

AF:

0.0420

AC:

445

AN:

10598

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0560

AC:

3808

AN:

68002

Other (OTH)

AF:

0.0356

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

286

572

859

1145

1431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0431

Hom.:

Bravo

AF:

0.0345

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.75

PhyloP100

-1.9

PromoterAI

-0.097

Neutral

(source)

Mutation Taster

=294/6

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