14-72352201-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001204424.2(RGS6):c.184+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 0.000513 in 1,607,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: RGS6 NM_001204424.2 splice_region, intron
• Scores: Splicing: ADA: 0.0004093
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-72352201-C-T is Benign according to our data. Variant chr14-72352201-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 707930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 418 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.184+7C>T		splice_region_variant, intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.184+7C>T		splice_region_variant, intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000800 AC: 199 AN: 248602 Hom.: 0 AF XY: 0.000640 AC XY: 86 AN XY: 134362

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000444

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000666

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000279 AC: 406 AN: 1455310 Hom.: 1 Cov.: 27 AF XY: 0.000253 AC XY: 183 AN XY: 724326

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.000517

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000632

Gnomad4 OTH exome AF: 0.000615

GnomAD4 genome AF: 0.00274 AC: 418 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74460

Gnomad4 AFR AF: 0.00938

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.00332

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 16, 2019	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.55
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.050
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

Other links and lift over

dbSNP: rs112696041; hg19: chr14-72818909;