Genetic Variant RGS7:c.*129G>A (chr1-240776091-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001364886.1(RGS7):c.*129G>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 0.0725 in 1,150,318 control chromosomes in the GnomAD database, including 3,479 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 0.061 ( 354 hom., cov: 32)

Exomes 𝑓: 0.074 ( 3125 hom. )

Consequence

RGS7
NM_001364886.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58

Publications

9 publications found

Variant links:

Genes affected

RGS7 (HGNC:10003): (regulator of G protein signaling 7) Enables G-protein beta-subunit binding activity and GTPase activator activity. Involved in positive regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGS7 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

RGS7 links:

ENSG00000226919 (HGNC:):

ENSG00000226919 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364886.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RGS7	NM_001364886.1	MANE Select	c.*129G>A	3_prime_UTR	Exon 19 of 19	NP_001351815.1
RGS7	NM_002924.6		c.*72G>A	3_prime_UTR	Exon 18 of 18	NP_002915.3
RGS7	NM_001282775.2		c.*129G>A	3_prime_UTR	Exon 18 of 18	NP_001269704.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RGS7	ENST00000440928.6	TSL:1 MANE Select	c.*129G>A	3_prime_UTR	Exon 19 of 19	ENSP00000404399.2
RGS7	ENST00000366565.5	TSL:1	c.*72G>A	3_prime_UTR	Exon 18 of 18	ENSP00000355523.1
RGS7	ENST00000366564.5	TSL:1	c.*72G>A	3_prime_UTR	Exon 17 of 17	ENSP00000355522.1

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9276

AN:

152090

Hom.:

353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.0868

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.0844

Gnomad FIN

AF:

0.0324

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0823

Gnomad OTH

AF:

0.0602

GnomAD4 exome

AF:

0.0742

AC:

74071

AN:

998110

Hom.:

3125

Cov.:

AF XY:

0.0754

AC XY:

39049

AN XY:

517592

show subpopulations

African (AFR)

AF:

0.0371

AC:

904

AN:

24384

American (AMR)

AF:

0.0389

AC:

1716

AN:

44112

Ashkenazi Jewish (ASJ)

AF:

0.0855

AC:

1990

AN:

23286

East Asian (EAS)

AF:

0.0165

AC:

620

AN:

37568

South Asian (SAS)

AF:

0.0920

AC:

7069

AN:

76836

European-Finnish (FIN)

AF:

0.0351

AC:

1868

AN:

53154

Middle Eastern (MID)

AF:

0.0901

AC:

442

AN:

4906

European-Non Finnish (NFE)

AF:

0.0818

AC:

56297

AN:

688582

Other (OTH)

AF:

0.0699

AC:

3165

AN:

45282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3557

7114

10672

14229

17786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1572

3144

4716

6288

7860

<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:

0.0610

AC:

9279

AN:

152208

Hom.:

354

Cov.:

AF XY:

0.0596

AC XY:

4435

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0390

AC:

1621

AN:

41524

American (AMR)

AF:

0.0458

AC:

700

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0868

AC:

301

AN:

3468

East Asian (EAS)

AF:

0.0244

AC:

126

AN:

5166

South Asian (SAS)

AF:

0.0839

AC:

405

AN:

4830

European-Finnish (FIN)

AF:

0.0324

AC:

343

AN:

10602

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0823

AC:

5595

AN:

68006

Other (OTH)

AF:

0.0610

AC:

129

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

450

900

1351

1801

2251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0757

Hom.:

611

Bravo

AF:

0.0599

Asia WGS

AF:

0.0620

AC:

218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

1.6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over