dbSNP rs12654812: RGS14:c.483+156G>A (chr5-177367190-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006480.5(RGS14):c.483+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,149,826 control chromosomes in the GnomAD database, including 71,030 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 0.34 ( 9048 hom., cov: 32)

Exomes 𝑓: 0.35 ( 61982 hom. )

Consequence

RGS14
NM_006480.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

79 publications found

Variant links:

Genes affected

RGS14 (HGNC:9996): (regulator of G protein signaling 14) This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases 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. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

RGS14 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=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS14	NM_006480.5 link	c.483+156G>A		intron_variant	Intron 5 of 14	ENST00000408923.8	NP_006471.2	O43566-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS14	ENST00000408923.8 link	c.483+156G>A		intron_variant	Intron 5 of 14	1	NM_006480.5	ENSP00000386229.3		O43566-7

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51956

AN:

151894

Hom.:

9039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.347

AC:

346718

AN:

997816

Hom.:

61982

Cov.:

AF XY:

0.350

AC XY:

173763

AN XY:

496398

show subpopulations

African (AFR)

AF:

0.323

AC:

7648

AN:

23650

American (AMR)

AF:

0.269

AC:

5782

AN:

21490

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

6418

AN:

17212

East Asian (EAS)

AF:

0.309

AC:

11094

AN:

35950

South Asian (SAS)

AF:

0.427

AC:

25525

AN:

59840

European-Finnish (FIN)

AF:

0.365

AC:

12499

AN:

34262

Middle Eastern (MID)

AF:

0.407

AC:

1219

AN:

2996

European-Non Finnish (NFE)

AF:

0.345

AC:

261289

AN:

758256

Other (OTH)

AF:

0.345

AC:

15244

AN:

44160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11669

23337

35006

46674

58343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7576

15152

22728

30304

37880

<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:

0.342

AC:

51998

AN:

152010

Hom.:

9048

Cov.:

AF XY:

0.341

AC XY:

25311

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.328

AC:

13613

AN:

41482

American (AMR)

AF:

0.319

AC:

4867

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1281

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1267

AN:

5152

South Asian (SAS)

AF:

0.416

AC:

2003

AN:

4816

European-Finnish (FIN)

AF:

0.367

AC:

3880

AN:

10584

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.355

AC:

24116

AN:

67920

Other (OTH)

AF:

0.327

AC:

691

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1736

3471

5207

6942

8678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.347

Hom.:

32016

Bravo

AF:

0.334

Asia WGS

AF:

0.326

AC:

1138

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.1

(source)

DANN

Benign

0.96

PhyloP100

-0.077

PromoterAI

-0.082

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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