Genetic Variant RGS7:c.609+46G>A (chr1-240868541-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001364886.1(RGS7):c.609+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,570,238 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0053 ( 40 hom. )

Consequence

RGS7
NM_001364886.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.344

Publications

1 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:

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=-0.82).

BP6

Variant 1-240868541-C-T is Benign according to our data. Variant chr1-240868541-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3250539.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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	UniProt
RGS7	NM_001364886.1	MANE Select	c.609+46G>A	intron	N/A	NP_001351815.1	P49802-1
RGS7	NM_002924.6		c.609+46G>A	intron	N/A	NP_002915.3
RGS7	NM_001282775.2		c.609+46G>A	intron	N/A	NP_001269704.1	P49802-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RGS7	ENST00000440928.6	TSL:1 MANE Select	c.609+46G>A	intron	N/A	ENSP00000404399.2	P49802-1
RGS7	ENST00000366565.5	TSL:1	c.609+46G>A	intron	N/A	ENSP00000355523.1	P49802-5
RGS7	ENST00000366564.5	TSL:1	c.609+46G>A	intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

484

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00575

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00367

AC:

921

AN:

251192

AF XY:

0.00359

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00391

Gnomad NFE exome

AF:

0.00567

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00530

AC:

7520

AN:

1417966

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

3711

AN XY:

708284

show subpopulations

African (AFR)

AF:

0.000919

AC:

AN:

32660

American (AMR)

AF:

0.00114

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.00396

AC:

338

AN:

85342

European-Finnish (FIN)

AF:

0.00469

AC:

249

AN:

53124

Middle Eastern (MID)

AF:

0.00282

AC:

AN:

5324

European-Non Finnish (NFE)

AF:

0.00603

AC:

6467

AN:

1072486

Other (OTH)

AF:

0.00628

AC:

370

AN:

58950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

412

824

1237

1649

2061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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:

0.00317

AC:

483

AN:

152272

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41570

American (AMR)

AF:

0.00124

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00229

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00575

AC:

391

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00366

Hom.:

Bravo

AF:

0.00309

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

(source)

DANN

Benign

0.84

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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