Genetic Variant RGS5:c.*2774C>A (chr1-163144568-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_003617.4(RGS5):c.*2774C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,328 control chromosomes in the GnomAD database, including 5,142 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 0.20 ( 5141 hom., cov: 32)

Exomes 𝑓: 0.075 ( 1 hom. )

Consequence

RGS5
NM_003617.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

Publications

7 publications found

Variant links:

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5 Gene-Disease associations (from GenCC):

essential hypertension, genetic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RGS5 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS5	NM_003617.4	MANE Select	c.*2774C>A	3_prime_UTR	Exon 5 of 5	NP_003608.1	O15539-1
RGS5	NM_001414472.1		c.*2774C>A	3_prime_UTR	Exon 7 of 7	NP_001401401.1
RGS5	NM_001414473.1		c.*2774C>A	3_prime_UTR	Exon 9 of 9	NP_001401402.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS5	ENST00000313961.10	TSL:1 MANE Select	c.*2774C>A	3_prime_UTR	Exon 5 of 5	ENSP00000319308.5	O15539-1
RGS5	ENST00000618415.4	TSL:4	c.*2774C>A	3_prime_UTR	Exon 6 of 6	ENSP00000480891.1	O15539-2
RGS5	ENST00000469495.5	TSL:5	n.167+7982C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30825

AN:

151756

Hom.:

5130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0978

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.0752

AC:

AN:

452

Hom.:

Cov.:

AF XY:

0.0839

AC XY:

AN XY:

274

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0704

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.203

AC:

30876

AN:

151876

Hom.:

5141

Cov.:

AF XY:

0.199

AC XY:

14746

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.460

AC:

19005

AN:

41360

American (AMR)

AF:

0.108

AC:

1644

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0640

AC:

222

AN:

3468

East Asian (EAS)

AF:

0.263

AC:

1355

AN:

5148

South Asian (SAS)

AF:

0.161

AC:

774

AN:

4800

European-Finnish (FIN)

AF:

0.0688

AC:

728

AN:

10578

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0979

AC:

6653

AN:

67974

Other (OTH)

AF:

0.175

AC:

368

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1045

2091

3136

4182

5227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.120

Hom.:

2391

Bravo

AF:

0.216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.099

(source)

DANN

Benign

0.55

PhyloP100

-0.76

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over