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GeneBe

1-240827155-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001364886.1(RGS7):c.627A>G(p.Thr209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,618 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 16 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

RGS7
NM_001364886.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.874
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-240827155-T-C is Benign according to our data. Variant chr1-240827155-T-C is described in ClinVar as [Benign]. Clinvar id is 787765.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.874 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00833 (1269/152344) while in subpopulation AFR AF= 0.0274 (1140/41578). AF 95% confidence interval is 0.0261. There are 16 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1268 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGS7NM_001364886.1 linkuse as main transcriptc.627A>G p.Thr209= synonymous_variant 10/19 ENST00000440928.6
LOC124904602XR_007067053.1 linkuse as main transcriptn.155+2137T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGS7ENST00000440928.6 linkuse as main transcriptc.627A>G p.Thr209= synonymous_variant 10/191 NM_001364886.1 P49802-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00833
AC:
1268
AN:
152226
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0275
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000962
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00241
AC:
607
AN:
251478
Hom.:
6
AF XY:
0.00189
AC XY:
257
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0278
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
Gnomad SAS exome
AF:
0.00157
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000202
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00110
AC:
1614
AN:
1461274
Hom.:
15
Cov.:
30
AF XY:
0.00101
AC XY:
734
AN XY:
727006
show subpopulations
Gnomad4 AFR exome
AF:
0.0273
Gnomad4 AMR exome
AF:
0.00235
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.00152
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000247
Gnomad4 OTH exome
AF:
0.00265
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00833
AC:
1269
AN:
152344
Hom.:
16
Cov.:
32
AF XY:
0.00797
AC XY:
594
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0274
Gnomad4 AMR
AF:
0.00484
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000964
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00464
Hom.:
4
Bravo
AF:
0.00992
Asia WGS
AF:
0.00779
AC:
27
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
1.6
Dann
Benign
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35467041; hg19: chr1-240990455; API