Variant 14-72352260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001204424.2(RGS6):c.184+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00941 in 1,195,978 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 64 hom. )

Consequence

RGS6
NM_001204424.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0830

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]

RGS6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-72352260-C-T is Benign according to our data. Variant chr14-72352260-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1293 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2 linkuse as main transcript	c.184+66C>T		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6 linkuse as main transcript	c.184+66C>T		intron_variant		2	NM_001204424.2	P1	P49758-3

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1292

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00956

GnomAD4 exome

AF:

0.00954

AC:

9961

AN:

1043738

Hom.:

AF XY:

0.00947

AC XY:

5037

AN XY:

531902

show subpopulations

Gnomad4 AFR exome

AF:

0.00485

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.00619

Gnomad4 EAS exome

AF:

0.000251

Gnomad4 SAS exome

AF:

0.000763

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00837

GnomAD4 genome

AF:

0.00849

AC:

1293

AN:

152240

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

619

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00438

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.3

DANN

Benign

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over