chr14-71964747-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001204424.2(RGS6):​c.-20-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,496,996 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 78 hom. )

Consequence

RGS6
NM_001204424.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
This place is a probable branch point but rather VUS (scored 5 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 14-71964747-A-G is Benign according to our data. Variant chr14-71964747-A-G is described in ClinVar as [Benign]. Clinvar id is 1182809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGS6NM_001204424.2 linkuse as main transcriptc.-20-25A>G intron_variant ENST00000553525.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGS6ENST00000553525.6 linkuse as main transcriptc.-20-25A>G intron_variant 2 NM_001204424.2 P1P49758-3

Frequencies

GnomAD3 genomes
AF:
0.0178
AC:
2704
AN:
152132
Hom.:
86
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0621
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00498
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00481
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00520
AC:
1182
AN:
227252
Hom.:
40
AF XY:
0.00358
AC XY:
441
AN XY:
123046
show subpopulations
Gnomad AFR exome
AF:
0.0656
Gnomad AMR exome
AF:
0.00211
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00599
Gnomad SAS exome
AF:
0.000315
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000375
Gnomad OTH exome
AF:
0.000557
GnomAD4 exome
AF:
0.00189
AC:
2545
AN:
1344746
Hom.:
78
Cov.:
18
AF XY:
0.00165
AC XY:
1111
AN XY:
672482
show subpopulations
Gnomad4 AFR exome
AF:
0.0689
Gnomad4 AMR exome
AF:
0.00259
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00263
Gnomad4 SAS exome
AF:
0.000192
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000255
Gnomad4 OTH exome
AF:
0.00375
GnomAD4 genome
AF:
0.0178
AC:
2711
AN:
152250
Hom.:
86
Cov.:
33
AF XY:
0.0171
AC XY:
1273
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0620
Gnomad4 AMR
AF:
0.00497
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00482
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.0138
Hom.:
9
Bravo
AF:
0.0202
Asia WGS
AF:
0.00346
AC:
13
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 06, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
15
DANN
Benign
0.65
BranchPoint Hunter
5.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs28678612; hg19: chr14-72431464; API