Genetic Variant RGS7:c.176-15346G>T (chr1-240998475-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001364886.1(RGS7):c.176-15346G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 996,262 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RGS7
NM_001364886.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

6 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:

ENSG00000238085 (HGNC:):

ENSG00000238085 links:

RPLP1P2 (HGNC:36210):

RPLP1P2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

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.176-15346G>T	intron	N/A	NP_001351815.1	P49802-1
RGS7	NM_002924.6		c.176-15346G>T	intron	N/A	NP_002915.3
RGS7	NM_001282775.2		c.176-15346G>T	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.176-15346G>T	intron	N/A	ENSP00000404399.2	P49802-1
RGS7	ENST00000366565.5	TSL:1	c.176-15346G>T	intron	N/A	ENSP00000355523.1	P49802-5
RGS7	ENST00000366564.5	TSL:1	c.176-15346G>T	intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

844280

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

443418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21390

American (AMR)

AF:

0.00

AC:

AN:

39102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20558

East Asian (EAS)

AF:

0.00

AC:

AN:

35432

South Asian (SAS)

AF:

0.00

AC:

AN:

72992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2730

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

578548

Other (OTH)

AF:

0.00

AC:

AN:

38740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.7

(source)

DANN

Benign

0.78

PhyloP100

2.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over