Genetic Variant NM_001204424.2:c.1423-9889A>G (chr14-72552528-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 NM_001204424.2(RGS6):c.1423-9889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,224 control chromosomes in the GnomAD database, including 2,986 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 0.19 ( 2985 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

RGS6
NM_001204424.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Publications

19 publications found

Variant links:

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

RGS6 links:

ENSG00000258871 (HGNC:):

ENSG00000258871 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 (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2 link	c.1423-9889A>G		intron_variant	Intron 17 of 17	ENST00000553525.6	NP_001191353.1	P49758-3Q2M3K2B7Z2A0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6 link	c.1423-9889A>G		intron_variant	Intron 17 of 17	2	NM_001204424.2	ENSP00000451030.1		P49758-3

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29051

AN:

152058

Hom.:

2990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

AF XY:

0.156

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0625

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.191

AC:

29052

AN:

152176

Hom.:

2985

Cov.:

AF XY:

0.191

AC XY:

14205

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.141

AC:

5846

AN:

41518

American (AMR)

AF:

0.207

AC:

3157

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

933

AN:

3468

East Asian (EAS)

AF:

0.147

AC:

761

AN:

5168

South Asian (SAS)

AF:

0.273

AC:

1314

AN:

4818

European-Finnish (FIN)

AF:

0.166

AC:

1762

AN:

10596

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.213

AC:

14458

AN:

68008

Other (OTH)

AF:

0.214

AC:

452

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1213

2427

3640

4854

6067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.211

Hom.:

15143

Bravo

AF:

0.190

Asia WGS

AF:

0.258

AC:

896

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.69

PhyloP100

-0.23

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over