dbSNP rs1323291: RGS1:c.*91T>G (chr1-192579413-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002922.4(RGS1):c.*91T>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 0.101 in 1,226,474 control chromosomes in the GnomAD database, including 9,264 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 0.16 ( 3224 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6040 hom. )

Consequence

RGS1
NM_002922.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

Publications

14 publications found

Variant links:

Genes affected

RGS1 (HGNC:9991): (regulator of G protein signaling 1) This gene encodes a member of the regulator of G-protein signalling family. This protein is located on the cytosolic side of the plasma membrane and contains a conserved, 120 amino acid motif called the RGS domain. The protein attenuates the signalling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

RGS1 links:

ENSG00000285280 (HGNC:49018): (RSG2 antisense RNA 1)

ENSG00000285280 links:

LOC105371664 (HGNC:):

LOC105371664 links:

Genome browser will be placed here

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=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS1	NM_002922.4 link	c.*91T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000367459.8	NP_002913.3	Q08116-1
LOC105371664	XR_002958418.2 link	n.288-12197A>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS1	ENST00000367459.8 link	c.*91T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_002922.4	ENSP00000356429.3		Q08116-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24143

AN:

151912

Hom.:

3219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0759

Gnomad FIN

AF:

0.0802

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0846

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.0930

AC:

99875

AN:

1074446

Hom.:

6040

Cov.:

AF XY:

0.0907

AC XY:

49327

AN XY:

544068

show subpopulations

African (AFR)

AF:

0.396

AC:

9569

AN:

24162

American (AMR)

AF:

0.0603

AC:

1566

AN:

25966

Ashkenazi Jewish (ASJ)

AF:

0.0454

AC:

967

AN:

21286

East Asian (EAS)

AF:

0.000139

AC:

AN:

36014

South Asian (SAS)

AF:

0.0734

AC:

4981

AN:

67870

European-Finnish (FIN)

AF:

0.0777

AC:

3949

AN:

50828

Middle Eastern (MID)

AF:

0.0689

AC:

333

AN:

4830

European-Non Finnish (NFE)

AF:

0.0929

AC:

74050

AN:

796708

Other (OTH)

AF:

0.0952

AC:

4455

AN:

46782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4205

8410

12616

16821

21026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2632

5264

7896

10528

13160

<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:

0.159

AC:

24172

AN:

152028

Hom.:

3224

Cov.:

AF XY:

0.155

AC XY:

11523

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.371

AC:

15370

AN:

41414

American (AMR)

AF:

0.0883

AC:

1348

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

166

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.0758

AC:

365

AN:

4816

European-Finnish (FIN)

AF:

0.0802

AC:

851

AN:

10606

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0846

AC:

5748

AN:

67966

Other (OTH)

AF:

0.113

AC:

239

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

917

1833

2750

3666

4583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.105

Hom.:

1736

Bravo

AF:

0.170

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.9

(source)

DANN

Benign

0.81

PhyloP100

0.21

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