dbSNP rs10921202: RGS1:c.281-300G>T (chr1-192577922-G-T) – 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.281-300G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 329,238 control chromosomes in the GnomAD database, including 682 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 0.053 ( 263 hom., cov: 32)

Exomes 𝑓: 0.063 ( 419 hom. )

Consequence

RGS1
NM_002922.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Publications

11 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS1	NM_002922.4 link	c.281-300G>T		intron_variant	Intron 3 of 4	ENST00000367459.8	NP_002913.3	Q08116-1
LOC105371664	XR_002958418.2 link	n.288-10706C>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS1	ENST00000367459.8 link	c.281-300G>T		intron_variant	Intron 3 of 4	1	NM_002922.4	ENSP00000356429.3		Q08116-1

Frequencies

GnomAD3 genomes

AF:

0.0531

AC:

8074

AN:

151984

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.0445

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0718

Gnomad OTH

AF:

0.0561

GnomAD4 exome

AF:

0.0629

AC:

11149

AN:

177136

Hom.:

419

Cov.:

AF XY:

0.0647

AC XY:

5963

AN XY:

92194

show subpopulations

African (AFR)

AF:

0.0226

AC:

127

AN:

5612

American (AMR)

AF:

0.0373

AC:

260

AN:

6964

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

644

AN:

6158

East Asian (EAS)

AF:

0.0225

AC:

278

AN:

12362

South Asian (SAS)

AF:

0.0790

AC:

1088

AN:

13766

European-Finnish (FIN)

AF:

0.0382

AC:

320

AN:

8384

Middle Eastern (MID)

AF:

0.0592

AC:

AN:

862

European-Non Finnish (NFE)

AF:

0.0689

AC:

7718

AN:

111974

Other (OTH)

AF:

0.0600

AC:

663

AN:

11054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

504

1009

1513

2018

2522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0532

AC:

8088

AN:

152102

Hom.:

263

Cov.:

AF XY:

0.0509

AC XY:

3782

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0210

AC:

873

AN:

41518

American (AMR)

AF:

0.0408

AC:

622

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3464

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5186

South Asian (SAS)

AF:

0.0978

AC:

471

AN:

4818

European-Finnish (FIN)

AF:

0.0445

AC:

472

AN:

10604

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0718

AC:

4879

AN:

67952

Other (OTH)

AF:

0.0575

AC:

121

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

391

782

1173

1564

1955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0666

Hom.:

712

Bravo

AF:

0.0500

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

(source)

DANN

Benign

0.49

PhyloP100

0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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