Variant 14-71964882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001204424.2(RGS6):c.84+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,611,602 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 31 hom. )

Consequence

RGS6
NM_001204424.2 splice_region, intron

Scores

Splicing: ADA: 0.0003081

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

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:

RGS6 (HGNC:):

RGS6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-71964882-C-T is Benign according to our data. Variant chr14-71964882-C-T is described in ClinVar as [Benign]. Clinvar id is 784289.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 749 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS6	NM_001204424.2 linkuse as main transcript	c.84+7C>T		splice_region_variant, intron_variant		ENST00000553525.6	NP_001191353.1	P49758-3Q2M3K2B7Z2A0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6 linkuse as main transcript	c.84+7C>T		splice_region_variant, intron_variant		2	NM_001204424.2	ENSP00000451030.1		P49758-3

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

751

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00507

AC:

1270

AN:

250618

Hom.:

AF XY:

0.00508

AC XY:

688

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00381

Gnomad ASJ exome

AF:

0.000796

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.00366

Gnomad NFE exome

AF:

0.00824

Gnomad OTH exome

AF:

0.00607

GnomAD4 exome

AF:

0.00678

AC:

9890

AN:

1459348

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

4752

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.000988

Gnomad4 AMR exome

AF:

0.00388

Gnomad4 ASJ exome

AF:

0.000881

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00808

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.00492

AC:

749

AN:

152254

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00801

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00522

Hom.:

Bravo

AF:

0.00528

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00753

EpiControl

AF:

0.00718

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 05, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.49

Position offset: -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