Genetic Variant RGS17:c.444+88G>A (chr6-153024174-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 NM_012419.5(RGS17):c.444+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 805,852 control chromosomes in the GnomAD database, including 206,761 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 0.76 ( 45399 hom., cov: 32)

Exomes 𝑓: 0.70 ( 161362 hom. )

Consequence

RGS17
NM_012419.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.921

Publications

8 publications found

Variant links:

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling 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]

RGS17 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012419.5. 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
	RGS17	NM_012419.5	MANE Select	c.444+88G>A		intron	N/A	NP_036551.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS17	ENST00000206262.2	TSL:1 MANE Select	c.444+88G>A	intron	N/A	ENSP00000206262.1	Q9UGC6
RGS17	ENST00000367225.6	TSL:1	c.444+88G>A	intron	N/A	ENSP00000356194.1	Q9UGC6
RGS17	ENST00000914255.1		c.354+88G>A	intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

116087

AN:

152030

Hom.:

45324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.942

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.716

GnomAD4 exome

AF:

0.700

AC:

457275

AN:

653704

Hom.:

161362

AF XY:

0.698

AC XY:

239988

AN XY:

343764

show subpopulations

African (AFR)

AF:

0.944

AC:

16007

AN:

16950

American (AMR)

AF:

0.764

AC:

22931

AN:

30008

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

11304

AN:

17766

East Asian (EAS)

AF:

0.621

AC:

20375

AN:

32822

South Asian (SAS)

AF:

0.749

AC:

42192

AN:

56338

European-Finnish (FIN)

AF:

0.729

AC:

31907

AN:

43776

Middle Eastern (MID)

AF:

0.687

AC:

1772

AN:

2578

European-Non Finnish (NFE)

AF:

0.684

AC:

287396

AN:

420284

Other (OTH)

AF:

0.705

AC:

23391

AN:

33182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

6964

13928

20892

27856

34820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3746

7492

11238

14984

18730

<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:

0.764

AC:

116224

AN:

152148

Hom.:

45399

Cov.:

AF XY:

0.764

AC XY:

56857

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.942

AC:

39127

AN:

41538

American (AMR)

AF:

0.752

AC:

11492

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2212

AN:

3470

East Asian (EAS)

AF:

0.566

AC:

2920

AN:

5162

South Asian (SAS)

AF:

0.755

AC:

3643

AN:

4822

European-Finnish (FIN)

AF:

0.751

AC:

7949

AN:

10586

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46391

AN:

67964

Other (OTH)

AF:

0.717

AC:

1512

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1301

2601

3902

5202

6503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.689

Hom.:

10613

Bravo

AF:

0.769

Asia WGS

AF:

0.715

AC:

2489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.56

(source)

DANN

Benign

0.54

PhyloP100

-0.92

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over