dbSNP rs2984920: RGS2-AS1:n.165-8449T>C (chr1-192575665-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000642855.1(RGS2-AS1):n.340-8449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,285,938 control chromosomes in the GnomAD database, including 445,381 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 0.86 ( 56441 hom., cov: 28)

Exomes 𝑓: 0.83 ( 388940 hom. )

Consequence

RGS2-AS1
ENST00000642855.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

30 publications found

Variant links:

Genes affected

RGS2-AS1 (HGNC:49018): (RSG2 antisense RNA 1)

RGS2-AS1 links:

LOC105371664 (HGNC:):

LOC105371664 links:

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:

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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=-0.47).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642855.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS1	NM_002922.4	MANE Select	c.-128A>G		upstream_gene	N/A	NP_002913.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
RGS2-AS1	ENST00000434300.3	TSL:5	n.165-8449T>C	intron	N/A
RGS2-AS1	ENST00000642855.1		n.340-8449T>C	intron	N/A
RGS2-AS1	ENST00000644058.2		n.565-8449T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

130256

AN:

151364

Hom.:

56385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.953

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.793

Gnomad SAS

AF:

0.913

Gnomad FIN

AF:

0.868

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.844

GnomAD4 exome

AF:

0.827

AC:

938239

AN:

1134460

Hom.:

388940

AF XY:

0.828

AC XY:

461846

AN XY:

557812

show subpopulations

African (AFR)

AF:

0.960

AC:

25094

AN:

26136

American (AMR)

AF:

0.753

AC:

18353

AN:

24382

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

14950

AN:

17314

East Asian (EAS)

AF:

0.769

AC:

28300

AN:

36786

South Asian (SAS)

AF:

0.896

AC:

46166

AN:

51544

European-Finnish (FIN)

AF:

0.859

AC:

35511

AN:

41354

Middle Eastern (MID)

AF:

0.845

AC:

3831

AN:

4534

European-Non Finnish (NFE)

AF:

0.821

AC:

725586

AN:

884196

Other (OTH)

AF:

0.839

AC:

40448

AN:

48214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7554

15108

22661

30215

37769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16954

33908

50862

67816

84770

<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:

0.861

AC:

130367

AN:

151478

Hom.:

56441

Cov.:

AF XY:

0.863

AC XY:

63796

AN XY:

73916

show subpopulations

African (AFR)

AF:

0.953

AC:

39407

AN:

41352

American (AMR)

AF:

0.805

AC:

12225

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

2979

AN:

3466

East Asian (EAS)

AF:

0.793

AC:

4088

AN:

5152

South Asian (SAS)

AF:

0.913

AC:

4374

AN:

4792

European-Finnish (FIN)

AF:

0.868

AC:

9001

AN:

10374

Middle Eastern (MID)

AF:

0.810

AC:

238

AN:

294

European-Non Finnish (NFE)

AF:

0.818

AC:

55524

AN:

67856

Other (OTH)

AF:

0.840

AC:

1763

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

878

1756

2633

3511

4389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.838

Hom.:

27643

Bravo

AF:

0.859

Asia WGS

AF:

0.873

AC:

3036

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

2.4

PromoterAI

-0.52

Under-expression

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over